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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>PHF6</italic> mutations in T-cell acute lymphoblastic leukemia</title><author><name sortKey="Van Vlierberghe, Pieter" sort="Van Vlierberghe, Pieter" uniqKey="Van Vlierberghe P" first="Pieter" last="Van Vlierberghe">Pieter Van Vlierberghe</name><affiliation><nlm:aff id="A1">Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Palomero, Teresa" sort="Palomero, Teresa" uniqKey="Palomero T" first="Teresa" last="Palomero">Teresa Palomero</name><affiliation><nlm:aff id="A1">Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Pathology, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Khiabanian, Hossein" sort="Khiabanian, Hossein" uniqKey="Khiabanian H" first="Hossein" last="Khiabanian">Hossein Khiabanian</name><affiliation><nlm:aff id="A5">Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Van Der Meulen, Joni" sort="Van Der Meulen, Joni" uniqKey="Van Der Meulen J" first="Joni" last="Van Der Meulen">Joni Van Der Meulen</name><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Castillo, Mireia" sort="Castillo, Mireia" uniqKey="Castillo M" first="Mireia" last="Castillo">Mireia Castillo</name><affiliation><nlm:aff id="A4">Department of Pathology, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Van Roy, Nadine" sort="Van Roy, Nadine" uniqKey="Van Roy N" first="Nadine" last="Van Roy">Nadine Van Roy</name><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="De Moerloose, Barbara" sort="De Moerloose, Barbara" uniqKey="De Moerloose B" first="Barbara" last="De Moerloose">Barbara De Moerloose</name><affiliation><nlm:aff id="A6">Department of Pediatric Hemato-Oncology, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Philippe, Jan" sort="Philippe, Jan" uniqKey="Philippe J" first="Jan" last="Philippé">Jan Philippé</name><affiliation><nlm:aff id="A7">Department of Clinical Chemistry, Immunology and Microbiology, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Gonzalez Garcia, Sara" sort="Gonzalez Garcia, Sara" uniqKey="Gonzalez Garcia S" first="Sara" last="González-García">Sara González-García</name><affiliation><nlm:aff id="A8">Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Toribio, Maria L" sort="Toribio, Maria L" uniqKey="Toribio M" first="María L" last="Toribio">María L. Toribio</name><affiliation><nlm:aff id="A8">Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Taghon, Tom" sort="Taghon, Tom" uniqKey="Taghon T" first="Tom" last="Taghon">Tom Taghon</name><affiliation><nlm:aff id="A7">Department of Clinical Chemistry, Immunology and Microbiology, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Zuurbier, Linda" sort="Zuurbier, Linda" uniqKey="Zuurbier L" first="Linda" last="Zuurbier">Linda Zuurbier</name><affiliation><nlm:aff id="A3">Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Cauwelier, Barbara" sort="Cauwelier, Barbara" uniqKey="Cauwelier B" first="Barbara" last="Cauwelier">Barbara Cauwelier</name><affiliation><nlm:aff id="A9">Department of Hematology, Hospital St-Jan, Bruges, Belgium</nlm:aff></affiliation></author><author><name sortKey="Harrison, Christine J" sort="Harrison, Christine J" uniqKey="Harrison C" first="Christine J" last="Harrison">Christine J. Harrison</name><affiliation><nlm:aff id="A10">Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, UK</nlm:aff></affiliation></author><author><name sortKey="Schwab, Claire" sort="Schwab, Claire" uniqKey="Schwab C" first="Claire" last="Schwab">Claire Schwab</name><affiliation><nlm:aff id="A10">Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, UK</nlm:aff></affiliation></author><author><name sortKey="Pisecker, Markus" sort="Pisecker, Markus" uniqKey="Pisecker M" first="Markus" last="Pisecker">Markus Pisecker</name><affiliation><nlm:aff id="A11">Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Strehl, Sabine" sort="Strehl, Sabine" uniqKey="Strehl S" first="Sabine" last="Strehl">Sabine Strehl</name><affiliation><nlm:aff id="A11">Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Langerak, Anton W" sort="Langerak, Anton W" uniqKey="Langerak A" first="Anton W" last="Langerak">Anton W. Langerak</name><affiliation><nlm:aff id="A12">Department of Immunology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Gecz, Jozef" sort="Gecz, Jozef" uniqKey="Gecz J" first="Jozef" last="Gecz">Jozef Gecz</name><affiliation><nlm:aff id="A13">Department of Genetics and Molecular Pathology, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Department of Pediatrics, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Sonneveld, Edwin" sort="Sonneveld, Edwin" uniqKey="Sonneveld E" first="Edwin" last="Sonneveld">Edwin Sonneveld</name><affiliation><nlm:aff id="A15">on behalf of the Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Pieters, Rob" sort="Pieters, Rob" uniqKey="Pieters R" first="Rob" last="Pieters">Rob Pieters</name><affiliation><nlm:aff id="A3">Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A15">on behalf of the Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Paietta, Elisabeth" sort="Paietta, Elisabeth" uniqKey="Paietta E" first="Elisabeth" last="Paietta">Elisabeth Paietta</name><affiliation><nlm:aff id="A16">Montefiore Medical Center North, Bronx, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Rowe, Jacob M" sort="Rowe, Jacob M" uniqKey="Rowe J" first="Jacob M" last="Rowe">Jacob M. Rowe</name><affiliation><nlm:aff id="A17">Rambam Medical Center and Technion, Israel Institute of Technology, Haifa, Israel</nlm:aff></affiliation></author><author><name sortKey="Wiernik, Peter H" sort="Wiernik, Peter H" uniqKey="Wiernik P" first="Peter H" last="Wiernik">Peter H. Wiernik</name><affiliation><nlm:aff id="A16">Montefiore Medical Center North, Bronx, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Benoit, Yves" sort="Benoit, Yves" uniqKey="Benoit Y" first="Yves" last="Benoit">Yves Benoit</name><affiliation><nlm:aff id="A6">Department of Pediatric Hemato-Oncology, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Soulier, Jean" sort="Soulier, Jean" uniqKey="Soulier J" first="Jean" last="Soulier">Jean Soulier</name><affiliation><nlm:aff id="A18">Hematology Laboratory APHP, INSERM U944, Hôpital Saint Louis, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Poppe, Bruce" sort="Poppe, Bruce" uniqKey="Poppe B" first="Bruce" last="Poppe">Bruce Poppe</name><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Yao, Xiaopan" sort="Yao, Xiaopan" uniqKey="Yao X" first="Xiaopan" last="Yao">Xiaopan Yao</name><affiliation><nlm:aff id="A19">Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Cordon Cardo, Carlos" sort="Cordon Cardo, Carlos" uniqKey="Cordon Cardo C" first="Carlos" last="Cordon-Cardo">Carlos Cordon-Cardo</name><affiliation><nlm:aff id="A4">Department of Pathology, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Meijerink, Jules" sort="Meijerink, Jules" uniqKey="Meijerink J" first="Jules" last="Meijerink">Jules Meijerink</name><affiliation><nlm:aff id="A3">Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Rabadan, Raul" sort="Rabadan, Raul" uniqKey="Rabadan R" first="Raul" last="Rabadan">Raul Rabadan</name><affiliation><nlm:aff id="A5">Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Speleman, Frank" sort="Speleman, Frank" uniqKey="Speleman F" first="Frank" last="Speleman">Frank Speleman</name><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Ferrando, Adolfo" sort="Ferrando, Adolfo" uniqKey="Ferrando A" first="Adolfo" last="Ferrando">Adolfo Ferrando</name><affiliation><nlm:aff id="A1">Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Pathology, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Department of Pediatrics, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20228800</idno><idno type="pmc">2847364</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847364</idno><idno type="RBID">PMC:2847364</idno><idno type="doi">10.1038/ng.542</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">002E01</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E01</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>PHF6</italic> mutations in T-cell acute lymphoblastic leukemia</title><author><name sortKey="Van Vlierberghe, Pieter" sort="Van Vlierberghe, Pieter" uniqKey="Van Vlierberghe P" first="Pieter" last="Van Vlierberghe">Pieter Van Vlierberghe</name><affiliation><nlm:aff id="A1">Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Palomero, Teresa" sort="Palomero, Teresa" uniqKey="Palomero T" first="Teresa" last="Palomero">Teresa Palomero</name><affiliation><nlm:aff id="A1">Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Pathology, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Khiabanian, Hossein" sort="Khiabanian, Hossein" uniqKey="Khiabanian H" first="Hossein" last="Khiabanian">Hossein Khiabanian</name><affiliation><nlm:aff id="A5">Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Van Der Meulen, Joni" sort="Van Der Meulen, Joni" uniqKey="Van Der Meulen J" first="Joni" last="Van Der Meulen">Joni Van Der Meulen</name><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Castillo, Mireia" sort="Castillo, Mireia" uniqKey="Castillo M" first="Mireia" last="Castillo">Mireia Castillo</name><affiliation><nlm:aff id="A4">Department of Pathology, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Van Roy, Nadine" sort="Van Roy, Nadine" uniqKey="Van Roy N" first="Nadine" last="Van Roy">Nadine Van Roy</name><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="De Moerloose, Barbara" sort="De Moerloose, Barbara" uniqKey="De Moerloose B" first="Barbara" last="De Moerloose">Barbara De Moerloose</name><affiliation><nlm:aff id="A6">Department of Pediatric Hemato-Oncology, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Philippe, Jan" sort="Philippe, Jan" uniqKey="Philippe J" first="Jan" last="Philippé">Jan Philippé</name><affiliation><nlm:aff id="A7">Department of Clinical Chemistry, Immunology and Microbiology, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Gonzalez Garcia, Sara" sort="Gonzalez Garcia, Sara" uniqKey="Gonzalez Garcia S" first="Sara" last="González-García">Sara González-García</name><affiliation><nlm:aff id="A8">Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Toribio, Maria L" sort="Toribio, Maria L" uniqKey="Toribio M" first="María L" last="Toribio">María L. Toribio</name><affiliation><nlm:aff id="A8">Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain</nlm:aff></affiliation></author><author><name sortKey="Taghon, Tom" sort="Taghon, Tom" uniqKey="Taghon T" first="Tom" last="Taghon">Tom Taghon</name><affiliation><nlm:aff id="A7">Department of Clinical Chemistry, Immunology and Microbiology, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Zuurbier, Linda" sort="Zuurbier, Linda" uniqKey="Zuurbier L" first="Linda" last="Zuurbier">Linda Zuurbier</name><affiliation><nlm:aff id="A3">Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Cauwelier, Barbara" sort="Cauwelier, Barbara" uniqKey="Cauwelier B" first="Barbara" last="Cauwelier">Barbara Cauwelier</name><affiliation><nlm:aff id="A9">Department of Hematology, Hospital St-Jan, Bruges, Belgium</nlm:aff></affiliation></author><author><name sortKey="Harrison, Christine J" sort="Harrison, Christine J" uniqKey="Harrison C" first="Christine J" last="Harrison">Christine J. Harrison</name><affiliation><nlm:aff id="A10">Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, UK</nlm:aff></affiliation></author><author><name sortKey="Schwab, Claire" sort="Schwab, Claire" uniqKey="Schwab C" first="Claire" last="Schwab">Claire Schwab</name><affiliation><nlm:aff id="A10">Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, UK</nlm:aff></affiliation></author><author><name sortKey="Pisecker, Markus" sort="Pisecker, Markus" uniqKey="Pisecker M" first="Markus" last="Pisecker">Markus Pisecker</name><affiliation><nlm:aff id="A11">Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Strehl, Sabine" sort="Strehl, Sabine" uniqKey="Strehl S" first="Sabine" last="Strehl">Sabine Strehl</name><affiliation><nlm:aff id="A11">Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria</nlm:aff></affiliation></author><author><name sortKey="Langerak, Anton W" sort="Langerak, Anton W" uniqKey="Langerak A" first="Anton W" last="Langerak">Anton W. Langerak</name><affiliation><nlm:aff id="A12">Department of Immunology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Gecz, Jozef" sort="Gecz, Jozef" uniqKey="Gecz J" first="Jozef" last="Gecz">Jozef Gecz</name><affiliation><nlm:aff id="A13">Department of Genetics and Molecular Pathology, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Department of Pediatrics, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Sonneveld, Edwin" sort="Sonneveld, Edwin" uniqKey="Sonneveld E" first="Edwin" last="Sonneveld">Edwin Sonneveld</name><affiliation><nlm:aff id="A15">on behalf of the Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Pieters, Rob" sort="Pieters, Rob" uniqKey="Pieters R" first="Rob" last="Pieters">Rob Pieters</name><affiliation><nlm:aff id="A3">Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A15">on behalf of the Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Paietta, Elisabeth" sort="Paietta, Elisabeth" uniqKey="Paietta E" first="Elisabeth" last="Paietta">Elisabeth Paietta</name><affiliation><nlm:aff id="A16">Montefiore Medical Center North, Bronx, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Rowe, Jacob M" sort="Rowe, Jacob M" uniqKey="Rowe J" first="Jacob M" last="Rowe">Jacob M. Rowe</name><affiliation><nlm:aff id="A17">Rambam Medical Center and Technion, Israel Institute of Technology, Haifa, Israel</nlm:aff></affiliation></author><author><name sortKey="Wiernik, Peter H" sort="Wiernik, Peter H" uniqKey="Wiernik P" first="Peter H" last="Wiernik">Peter H. Wiernik</name><affiliation><nlm:aff id="A16">Montefiore Medical Center North, Bronx, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Benoit, Yves" sort="Benoit, Yves" uniqKey="Benoit Y" first="Yves" last="Benoit">Yves Benoit</name><affiliation><nlm:aff id="A6">Department of Pediatric Hemato-Oncology, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Soulier, Jean" sort="Soulier, Jean" uniqKey="Soulier J" first="Jean" last="Soulier">Jean Soulier</name><affiliation><nlm:aff id="A18">Hematology Laboratory APHP, INSERM U944, Hôpital Saint Louis, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Poppe, Bruce" sort="Poppe, Bruce" uniqKey="Poppe B" first="Bruce" last="Poppe">Bruce Poppe</name><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Yao, Xiaopan" sort="Yao, Xiaopan" uniqKey="Yao X" first="Xiaopan" last="Yao">Xiaopan Yao</name><affiliation><nlm:aff id="A19">Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Cordon Cardo, Carlos" sort="Cordon Cardo, Carlos" uniqKey="Cordon Cardo C" first="Carlos" last="Cordon-Cardo">Carlos Cordon-Cardo</name><affiliation><nlm:aff id="A4">Department of Pathology, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Meijerink, Jules" sort="Meijerink, Jules" uniqKey="Meijerink J" first="Jules" last="Meijerink">Jules Meijerink</name><affiliation><nlm:aff id="A3">Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Rabadan, Raul" sort="Rabadan, Raul" uniqKey="Rabadan R" first="Raul" last="Rabadan">Raul Rabadan</name><affiliation><nlm:aff id="A5">Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Speleman, Frank" sort="Speleman, Frank" uniqKey="Speleman F" first="Frank" last="Speleman">Frank Speleman</name><affiliation><nlm:aff id="A2">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Ferrando, Adolfo" sort="Ferrando, Adolfo" uniqKey="Ferrando A" first="Adolfo" last="Ferrando">Adolfo Ferrando</name><affiliation><nlm:aff id="A1">Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Pathology, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">Department of Pediatrics, Columbia University Medical Center, New York, New York, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Nature genetics</title><idno type="ISSN">1061-4036</idno><idno type="eISSN">1546-1718</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer<xref rid="R1" ref-type="bibr">1</xref>,<xref rid="R2" ref-type="bibr">2</xref>. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males<xref rid="R3" ref-type="bibr">3</xref>. In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (<italic>PHF6</italic>) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, <italic>PHF6</italic> mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of <italic>PHF6</italic> is significantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes <italic>TLX1</italic> and <italic>TLX3</italic>. Overall, these results identify <italic>PHF6</italic> as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between <italic>PHF6</italic> loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Carrel, L" uniqKey="Carrel L">L Carrel</name></author><author><name sortKey="Cottle, Aa" uniqKey="Cottle A">AA Cottle</name></author><author><name sortKey="Goglin, Kc" uniqKey="Goglin K">KC Goglin</name></author><author><name sortKey="Willard, Hf" uniqKey="Willard H">HF Willard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carrel, L" uniqKey="Carrel L">L Carrel</name></author><author><name sortKey="Willard, Hf" uniqKey="Willard H">HF Willard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goldberg, Jm" uniqKey="Goldberg J">JM Goldberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aifantis, I" uniqKey="Aifantis I">I Aifantis</name></author><author><name sortKey="Raetz, E" uniqKey="Raetz E">E Raetz</name></author><author><name sortKey="Buonamici, S" uniqKey="Buonamici S">S Buonamici</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pui, Ch" uniqKey="Pui C">CH Pui</name></author><author><name sortKey="Robison, Ll" uniqKey="Robison L">LL Robison</name></author><author><name sortKey="Look, At" uniqKey="Look A">AT Look</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gnirke, A" uniqKey="Gnirke A">A Gnirke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lower, Km" uniqKey="Lower K">KM Lower</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Borjeson, M" uniqKey="Borjeson M">M Borjeson</name></author><author><name sortKey="Forssman, H" uniqKey="Forssman H">H Forssman</name></author><author><name sortKey="Lehmann, O" uniqKey="Lehmann O">O Lehmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Turner, G" uniqKey="Turner G">G Turner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baker, La" uniqKey="Baker L">LA Baker</name></author><author><name sortKey="Allis, Cd" uniqKey="Allis C">CD Allis</name></author><author><name sortKey="Wang, Gg" uniqKey="Wang G">GG Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dephoure, N" uniqKey="Dephoure N">N Dephoure</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsuoka, S" uniqKey="Matsuoka S">S Matsuoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lowndes, Nf" uniqKey="Lowndes N">NF Lowndes</name></author><author><name sortKey="Toh, Gw" uniqKey="Toh G">GW Toh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Payer, B" uniqKey="Payer B">B Payer</name></author><author><name sortKey="Lee, Jt" uniqKey="Lee J">JT Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carrel, L" uniqKey="Carrel L">L Carrel</name></author><author><name sortKey="Willard, Hf" uniqKey="Willard H">HF Willard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferrando, Aa" uniqKey="Ferrando A">AA Ferrando</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soulier, J" uniqKey="Soulier J">J Soulier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Vlierberghe, P" uniqKey="Van Vlierberghe P">P Van Vlierberghe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Grotel, M" uniqKey="Van Grotel M">M van Grotel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marks, Di" uniqKey="Marks D">DI Marks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rumble, Sm" uniqKey="Rumble S">SM Rumble</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khiabanian, H" uniqKey="Khiabanian H">H Khiabanian</name></author><author><name sortKey="Vanvlierberghe, P" uniqKey="Vanvlierberghe P">P VanVlierberghe</name></author><author><name sortKey="Palomero, T" uniqKey="Palomero T">T Palomero</name></author><author><name sortKey="Ferrando, Aa" uniqKey="Ferrando A">AA Ferrando</name></author><author><name sortKey="Rabadan, R" uniqKey="Rabadan R">R Rabadan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clappier, E" uniqKey="Clappier E">E Clappier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Erdogan, F" uniqKey="Erdogan F">F Erdogan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lahortiga, I" uniqKey="Lahortiga I">I Lahortiga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Voss, Ak" uniqKey="Voss A">AK Voss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gonzalez Garcia, S" uniqKey="Gonzalez Garcia S">S Gonzalez-Garcia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moffat, J" uniqKey="Moffat J">J Moffat</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9216904</journal-id><journal-id journal-id-type="pubmed-jr-id">2419</journal-id><journal-id journal-id-type="nlm-ta">Nat Genet</journal-id><journal-id journal-id-type="iso-abbrev">Nat. Genet.</journal-id><journal-title-group><journal-title>Nature genetics</journal-title></journal-title-group><issn pub-type="ppub">1061-4036</issn><issn pub-type="epub">1546-1718</issn></journal-meta><article-meta><article-id pub-id-type="pmid">20228800</article-id><article-id pub-id-type="pmc">2847364</article-id><article-id pub-id-type="doi">10.1038/ng.542</article-id><article-id pub-id-type="manuscript">NIHMS176587</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title><italic>PHF6</italic> mutations in T-cell acute lymphoblastic leukemia</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Van Vlierberghe</surname><given-names>Pieter</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Palomero</surname><given-names>Teresa</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Khiabanian</surname><given-names>Hossein</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Van der Meulen</surname><given-names>Joni</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Castillo</surname><given-names>Mireia</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Van Roy</surname><given-names>Nadine</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>De Moerloose</surname><given-names>Barbara</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Philippé</surname><given-names>Jan</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>González-García</surname><given-names>Sara</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Toribio</surname><given-names>María L</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Taghon</surname><given-names>Tom</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Zuurbier</surname><given-names>Linda</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cauwelier</surname><given-names>Barbara</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Harrison</surname><given-names>Christine J</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Schwab</surname><given-names>Claire</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Pisecker</surname><given-names>Markus</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Strehl</surname><given-names>Sabine</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Langerak</surname><given-names>Anton W</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Gecz</surname><given-names>Jozef</given-names></name><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Sonneveld</surname><given-names>Edwin</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Pieters</surname><given-names>Rob</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Paietta</surname><given-names>Elisabeth</given-names></name><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Rowe</surname><given-names>Jacob M</given-names></name><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Wiernik</surname><given-names>Peter H</given-names></name><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Benoit</surname><given-names>Yves</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Soulier</surname><given-names>Jean</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Poppe</surname><given-names>Bruce</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Yao</surname><given-names>Xiaopan</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Cordon-Cardo</surname><given-names>Carlos</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Meijerink</surname><given-names>Jules</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rabadan</surname><given-names>Raul</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Speleman</surname><given-names>Frank</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Ferrando</surname><given-names>Adolfo</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A20">20</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib></contrib-group><aff id="A1"><label>1</label>Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA</aff><aff id="A2"><label>2</label>Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</aff><aff id="A3"><label>3</label>Department of Pediatric Oncology/Hematology, Erasmus MC, Rotterdam, The Netherlands</aff><aff id="A4"><label>4</label>Department of Pathology, Columbia University Medical Center, New York, New York, USA</aff><aff id="A5"><label>5</label>Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA</aff><aff id="A6"><label>6</label>Department of Pediatric Hemato-Oncology, Ghent University Hospital, Ghent, Belgium</aff><aff id="A7"><label>7</label>Department of Clinical Chemistry, Immunology and Microbiology, Ghent University Hospital, Ghent, Belgium</aff><aff id="A8"><label>8</label>Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain</aff><aff id="A9"><label>9</label>Department of Hematology, Hospital St-Jan, Bruges, Belgium</aff><aff id="A10"><label>10</label>Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, UK</aff><aff id="A11"><label>11</label>Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria</aff><aff id="A12"><label>12</label>Department of Immunology, Erasmus MC, Rotterdam, The Netherlands</aff><aff id="A13"><label>13</label>Department of Genetics and Molecular Pathology, University of Adelaide, Adelaide, Australia</aff><aff id="A14"><label>14</label>Department of Pediatrics, University of Adelaide, Adelaide, Australia</aff><aff id="A15"><label>15</label>on behalf of the Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands</aff><aff id="A16"><label>16</label>Montefiore Medical Center North, Bronx, New York, USA</aff><aff id="A17"><label>17</label>Rambam Medical Center and Technion, Israel Institute of Technology, Haifa, Israel</aff><aff id="A18"><label>18</label>Hematology Laboratory APHP, INSERM U944, Hôpital Saint Louis, Paris, France</aff><aff id="A19"><label>19</label>Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USA</aff><aff id="A20"><label>20</label>Department of Pediatrics, Columbia University Medical Center, New York, New York, USA</aff><author-notes><corresp id="FN1">Correspondence should be addressed to A.F. (<email>af2196@columbia.edu</email>)</corresp><fn id="FN2" fn-type="equal"><label>*</label><p>These authors contributed equally to this work.</p></fn><fn id="FN3"><label>†</label><p>These authors jointly directed the project.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>10</day><month>3</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>14</day><month>3</month><year>2010</year></pub-date><pub-date pub-type="ppub"><month>4</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>10</month><year>2010</year></pub-date><volume>42</volume><issue>4</issue><fpage>338</fpage><lpage>342</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ng.542</pmc-comment>
<permissions><license><license-p>Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: <ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link></license-p></license></permissions><abstract><p id="P1">Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer<xref rid="R1" ref-type="bibr">1</xref>,<xref rid="R2" ref-type="bibr">2</xref>. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males<xref rid="R3" ref-type="bibr">3</xref>. In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (<italic>PHF6</italic>) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, <italic>PHF6</italic> mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of <italic>PHF6</italic> is significantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes <italic>TLX1</italic> and <italic>TLX3</italic>. Overall, these results identify <italic>PHF6</italic> as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between <italic>PHF6</italic> loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.</p></abstract></article-meta></front><body><p id="P2">T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy in which multiple genetic defects collaborate in the transformation of T-cell progenitors<xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R5" ref-type="bibr">5</xref>. Notably, T-ALL has a 3-fold higher incidence in males<xref rid="R3" ref-type="bibr">3</xref>, while other immature hematologic tumors such as precursor B-lineage ALL (BCP-B-ALL) are equally frequent in males and females<xref rid="R3" ref-type="bibr">3</xref>.</p><p id="P3">To identify a possible X-linked tumor suppressor in T-ALL, we performed an X chromosome targeted mutation analysis in tumor DNA samples from 12 male T-ALL cases. For each sample, we performed in-solution DNA capture of 7,674 regions encompassing 3,045,708 nucleotides corresponding to 5,215 X chromosome exons using the Agilent Sure Select oligonucleotide capture system<xref rid="R6" ref-type="bibr">6</xref>. DNA samples enriched for X chromosome exons were then analyzed by next generation sequencing using the SOLiD 3 platform. This analysis identified 66 candidate novel non-synonymous single nucleotide variants and 7 positions with high confidence calls for containing complex variants such as insertions or deletions (<xref rid="F1" ref-type="fig">Fig. 1a</xref>). Dideoxynucleotide DNA sequencing of PCR products encompassing affected exons confirmed the presence of 61/66 (92%) of these single nucleotide variants and 4/7 (57%) of the more complex variants, including 2 insertions and 2 deletions (<xref rid="SD1" ref-type="supplementary-material">Supplementary Tables 1 and 2</xref>). Sequence analysis of paired DNA samples obtained at the time of clinical remission showed that most of these variants corresponded to previously unreported germline polymorphisms. However, and most notably, we also identified three somatically acquired changes corresponding to two non-synonymous single nucleotide substitutions (c.902A>G, p.T300A and c.990A>G, p.H330R) and a frameshift-creating insertion of 5 nucleotides (c.124_125insAGGCA, p.H43fs) in the <italic>PHF6</italic> (plant homeodomain finger 6) gene (<xref rid="F1" ref-type="fig">Fig. 1a</xref>).</p><p id="P4">In a complementary approach, we analyzed X chromosome array comparative genome hybridization (array-CGH) data from 246 primary T-ALL samples (179 male and 67 female) in a multi-centre setting. These analyses revealed the presence of recurrent deletions in chromosomal band Xq26 in 8 out of 246 (∼3%) T-ALL samples (<xref rid="T1" ref-type="table">Table 1</xref>). For 3 del(X)(q26) positive T-ALL cases, we performed array-CGH analysis against the corresponding remission material, which showed that these Xq26 deletions are somatically acquired leukemia-associated genetic events (<xref rid="T1" ref-type="table">Table 1</xref>). Re-analysis of all 8 del(X)(q26) positive T-ALL cases on a custom high-resolution chromosome X oligonucleotide array (<xref rid="F1" ref-type="fig">Fig. 1b,c</xref>) narrowed down the common minimally deleted region to an area of 80 kb containing the <italic>PHF6</italic> gene. Consistently, quantitative PCR analysis confirmed loss of the <italic>PHF6</italic> locus in the del(X)(q26) positive cases (<xref rid="F1" ref-type="fig">Fig. 1d</xref>). The convergent findings of our X chromosome exon mutation analysis and analysis of copy number alterations by array-CGH thus identified the <italic>PHF6</italic> gene as a new tumor suppressor mutated and deleted in T-ALL.</p><p id="P5"><italic>PHF6</italic> encodes a plant homeodomain (PHD) factor containing four nuclear localization signals and two imperfect PHD zinc finger domains<xref rid="R7" ref-type="bibr">7</xref> with a proposed role in the control of gene expression<xref rid="R7" ref-type="bibr">7</xref>. Notably, inactivating mutations in <italic>PHF6</italic> cause the Börjeson-Forssman-Lehmann syndrome (BFLS; MIM#301900), a relatively uncommon type of X-linked familial syndromic mental retardation which has not been associated with increased incidence of T-ALL<xref rid="R7" ref-type="bibr">7</xref>-<xref rid="R9" ref-type="bibr">9</xref>. Quantitative RT-PCR analysis demonstrated ubiquitous expression of <italic>PHF6</italic> transcripts in human tissues, with the highest levels of expression in thymus, ovary and thyroid and moderate levels of expression in spleen, testes and adipose tissue (<xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. 1</xref>). Consistent with these results, PHF6 was readily detected by immunohistochemistry in mouse thymus (<xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. 1</xref>). Finally, quantitative RT-PCR analysis of human thymocyte populations at different stages of development showed variable levels of <italic>PHF6</italic> expression, with marked upregulation of <italic>PHF6</italic> transcripts in CD4/CD8 double positive cells (<xref rid="SD1" ref-type="supplementary-material">Supplementary Fig. 1</xref>).</p><p id="P6">Mutation analysis of <italic>PHF6</italic> in an extended panel of pediatric and adult T-ALL primary samples identified truncating or missense mutations in <italic>PHF6</italic> in 38% (16/42) of adult and ∼16% (14/89) of pediatric T-ALL samples (<xref rid="F2" ref-type="fig">Fig. 2a</xref> and <xref rid="T1" ref-type="table">Table 1</xref>). In all available cases (7/30), analysis of matched buccal and/or bone marrow remission genomic DNA confirmed the somatic origin of <italic>PHF6</italic> mutations (4/21 frameshift mutations and 3/9 missense mutations) (<xref rid="F2" ref-type="fig">Fig. 2b</xref> and <xref rid="T1" ref-type="table">Table 1</xref>). Finally, no mutations in <italic>PHF6</italic> were identified in DNA samples from BCP-B-ALLs (<italic>n</italic> = 62), suggesting that mutational loss of <italic>PHF6</italic> in lymphoid tumors could be restricted to T-ALL.</p><p id="P7">Nonsense and frame-shift mutations accounted for 70% (21/30) of all <italic>PHF6</italic> mutations identified in our series and were evenly distributed throughout the gene. Missense mutations accounted for the remaining 30% (9/30) of <italic>PHF6</italic> lesions and recurrently involved codon C215 and the second zinc finger domain of the protein (<xref rid="F2" ref-type="fig">Fig. 2a</xref>). DNA sequence analysis of <italic>PHF6</italic> in a panel of 15 well characterized T-ALL cell lines (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 3</xref>) showed the presence of truncating mutations in the <italic>PHF6</italic> gene in the DND41, HPB-ALL and T-ALL1 cell lines. Western blot analysis and immunohistochemical staining of PHF6 demonstrated robust expression and nuclear localization of PHF6 in <italic>PHF6</italic>-wild-type tumors and complete loss of PHF6 protein in T-ALL cell lines harboring mutations in <italic>PHF6</italic> (<xref rid="F2" ref-type="fig">Fig. 2c,d</xref>).</p><p id="P8">PHD finger-containing proteins have been implicated in numerous cellular functions, including transcriptional regulation and in some instances as specialized reader modules that recognize the methylation status of histone lysine residues<xref rid="R10" ref-type="bibr">10</xref>. In addition, PHF6 has been reported to be phosphorylated during mitosis<xref rid="R11" ref-type="bibr">11</xref> and by the ATM and ATR kinases upon DNA damage<xref rid="R12" ref-type="bibr">12</xref>, which suggests a dynamic regulation of PHF6 during cell cycle and DNA repair. Consistent with this notion, shRNA knockdown of PHF6 resulted in increased levels of phosphorylated H2AX (gamma-H2AX), a posttranslational modification associated with the presence of DNA double strand breaks<xref rid="R13" ref-type="bibr">13</xref> (<xref rid="F2" ref-type="fig">Fig. 2e</xref>).</p><p id="P9">Sex determination in humans is controlled by differential representation of the X and Y chromosomes, with presence of an XY pair in the male genome and two copies of chromosome X in females. The presence of numerous genes in the non-autosomal region of the X chromosome could result in a genetic imbalance between male and female cells, which is compensated by random chromosomal inactivation of one copy of chromosome X in female cells<xref rid="R14" ref-type="bibr">14</xref>. However, allelic expression analysis has shown that some genes can escape X chromosome inactivation in certain tissues<xref rid="R1" ref-type="bibr">1</xref>,<xref rid="R2" ref-type="bibr">2</xref>,<xref rid="R15" ref-type="bibr">15</xref>. To test the possibility that <italic>PHF6</italic> could escape X-inactivation in T-ALL cells, we performed allelic expression analysis of a silent SNP (rs17317724) located in the 3′ untranslated region of <italic>PHF6</italic> in lymphoblasts from 3 informative female T-ALL cases. In each of these samples, <italic>PHF6</italic> was monoallelilically expressed, suggesting that biallelic expression of <italic>PHF6</italic> is not commonly found in T-ALL (<xref rid="F3" ref-type="fig">Fig. 3a</xref>). Most notably, we found that <italic>PHF6</italic> mutations are almost exclusively found in male T-ALL cases. <italic>PHF6</italic> mutations were present in 29/92 (32%) males and only in 1/39 (∼2.5%) females (P < 0.001; <xref rid="F3" ref-type="fig">Fig. 3b</xref> and <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>). Moreover, all 8 <italic>PHF6</italic> deletions identified by array-CGH analysis were found in male T-ALL cases, and each of the three cell lines with mutations in <italic>PHF6</italic> were derived from male T-ALL cases.</p><p id="P10">Immunohistochemical analysis of PHF6 expression in wild-type primary T-ALL samples showed positive PHF6 immunostaining (<italic>n</italic> = 5; 3 males and 2 females), while cases with <italic>PHF6</italic> truncating mutations (<italic>n</italic> = 4) (<xref rid="F3" ref-type="fig">Fig. 3c</xref>) or a point mutation in C215 (p.C215F) were negative for PHF6 protein expression (<xref rid="F3" ref-type="fig">Fig. 3c</xref>). In contrast, primary T-ALL cells harboring a <italic>PHF6</italic> point mutation in the PHD2 domain (p.T300A) were positive for PHF6 protein expression (<xref rid="F3" ref-type="fig">Fig. 3c</xref>). Overall, these results suggest that truncating mutations and point mutations in C215 impair PHF6 expression, while amino acid substitutions in the PHD2 domain of PHF6 may selectively impair the tumor suppressor function of this protein.</p><p id="P11">Leukemic transformation of immature thymocytes is the result of a multistep process involving numerous genetic abnormalities, which can be associated with different clinical features, including age and prognosis. Notably, <italic>PHF6</italic> mutations were significantly more prevalent in adult (16/42; 38%) than in pediatric T-ALLs (14/89; 16%) (<italic>P</italic> = 0.005; <xref rid="F4" ref-type="fig">Fig. 4a</xref>). Detailed genetic information was available for T-ALL cases treated in DCOG clinical trials (<italic>n</italic> = 65) (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 5</xref>). In this cohort, <italic>PHF6</italic> mutations were significantly associated with the aberrant expression of <italic>TLX1</italic> and <italic>TLX3</italic> (<italic>P</italic> < 0.005; <xref rid="F4" ref-type="fig">Fig. 4b</xref> and <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 5</xref>), two related oncogenes activated by chromosomal translocations in T-ALL<xref rid="R16" ref-type="bibr">16</xref>-<xref rid="R18" ref-type="bibr">18</xref>. No significant associations were observed between <italic>PHF6</italic> mutations and mutations in <italic>NOTCH1</italic>, <italic>FBXW7</italic> or <italic>PTEN</italic> in either pediatric (<italic>n</italic> = 65) or adult (<italic>n</italic> = 34) T-ALL cohorts (<xref rid="SD1" ref-type="supplementary-material">Supplementary Tables 5 and 6</xref>). Overall survival in <italic>PHF6</italic> wild-type pediatric T-ALL cases treated on DCOG protocols<xref rid="R19" ref-type="bibr">19</xref> was 65% (33/51) vs. 71% (10/14) for <italic>PHF6</italic>-mutated cases (log-rank <italic>P</italic> = 0.71) (<xref rid="F4" ref-type="fig">Fig. 4c</xref>). Overall survival in <italic>PHF6</italic> wild-type adult T-ALL leukemias treated in the ECOG2993 clinical trial was 36% (7/12) vs. 58% (8/22) for <italic>PHF6</italic>-mutated samples (log-rank <italic>P</italic> = 0.24) (<xref rid="F4" ref-type="fig">Fig. 4d</xref>).</p><p id="P12">Overall, these results identify <italic>PHF6</italic> as a new X-linked tumor suppressor gene and strongly suggest a specific interaction between the oncogenic programs activated by aberrant expression of TLX transcription factors and the mutational loss of <italic>PHF6</italic> in the pathogenesis of T-ALL.</p><sec sec-type="supplementary-material" id="S13"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>supp info</label><media xlink:href="NIHMS176587-supplement-supp_info.pdf" mimetype="application" mime-subtype="pdf" xlink:type="simple" id="d37e844" position="anchor"></media></supplementary-material><supplementary-material content-type="local-data" id="SD2"><media xlink:href="NIHMS176587-supplement-supplement_1.pdf" mimetype="application" mime-subtype="pdf" xlink:type="simple" id="d37e846" position="anchor"></media></supplementary-material></sec></body><back><ack id="S15"><p>This study was supported by the Fund for Scientific Research (FWO) Flanders (postdoctoral grants to P.V.V. and T.T., PhD grant to J.V.M., senior clinical investigator award to B.P. and project grants G.0198.08 and G.0869.10N to F.S.); the GOA-UGent (grant no. 12051203); the IWT-Vlaanderen (SBO grant no. 060848); the Children Cancer Fund Ghent (F.S.); Leukemia Research UK (C.H.); the Stichting Kinderen Kankervrij (KiKa; Grant no. KiKa 2007-012 to L.Z.); the Belgian Program of Interuniversity Poles of Attraction; the Belgian Foundation Against Cancer; the Austrian Ministry of Science and Research (GEN-AU Child, GZ 200.136/1-VI/1/2005 to S.S.), the National Library of Medicine (1R01LM010140-01 to R.R. and H.K.); the ECOG and DCOG tumor banks; grants from Plan Nacional (BFU 2007-60990 and PlanE2009-0110 to M.L.T.), Comunidad de Madrid (S-SAL0304-2006 to M.L.T), Fundación MM (M.L.T), Instituto de Salud Carlos III (RECAVA RD06/0014/1012 to M.L.T), an Institutional Grant from the Fundación Ramón Areces (M.L.T.), the Alex's Lemonade Stand Foundation Young Investigator Award (T.P.); a Northeast Biodefence Center ARRA award (U54-AI057158 to R.R.); the National Institutes of Health (R01CA120196 and R01CA129382 to A.F.); the Rally Across America Foundation (A.F); the Swim Across America Foundation (A.F.) and the Golfers Against Cancer Foundation (A.F.). A.F. is a Leukemia & Lymphoma Society Scholar. We thank the Pediatric Cardiosurgery Units from Centro Especial Ramón y Cajal and Ciudad Sanitaria La Paz (Madrid, Spain) for thymus samples.</p></ack><fn-group><fn id="FN4" fn-type="con"><p><bold>AUTHOR CONTRIBUTIONS:</bold> P.V.V. performed array CGH and mutation analysis of <italic>PHF6</italic> and wrote the manuscript. T.P. performed exon capture and next-generation sequencing of T-ALL samples and wrote the manuscript. H.K. analyzed next-generation sequencing data. J.V.d.M. performed additional array-CGH analysis and <italic>PHF6</italic> mutation screening in T-ALL and BCP-ALL samples. T.T., N.V.R. and A.W.L. performed experiments. M.C. and C.C.-C. performed and analyzed histological and immunohistochemical staining. J.P collaborated on <italic>PHF6</italic> mutation screening in BCP-ALL samples. C.J.H. and C.S. collaborated on additional screening for genomic <italic>PHF6</italic> deletions in T-ALL. Y.B., B.D.M and B.C. collaborated on the <italic>PHF6</italic> mutation screening. R.P. M.P., S.S. and J.S. collaborated on the multi-center array-CGH study. S.G.-G. and M.L.T. performed the isolation of T-cell progenitor cells for expression analysis of <italic>PHF6</italic>. X.Y. performed survival analysis of ECOG T-ALL patients. J.G. provided critical reagents and discussion. E.S. provided samples and correlative clinical data from DCOG. E.P., J.M.R. and P.H.W. provided samples and correlative clinical data from ECOG. J.M. and L.Z. collaborated on the multi-center array-CGH study and <italic>PHF6</italic> mutation analysis, provided molecular data on the characterization of T-ALL and performed survival analysis of <italic>PHF6</italic> mutations in the DCOG series. R.R. designed and directed the analysis of next generation sequencing results. F.S. and B.P. designed the studies and directed research. A.F. designed the studies, directed research and wrote the manuscript.</p></fn></fn-group><ref-list><ref id="R1"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Carrel</surname><given-names>L</given-names></name><name><surname>Cottle</surname><given-names>AA</given-names></name><name><surname>Goglin</surname><given-names>KC</given-names></name><name><surname>Willard</surname><given-names>HF</given-names></name></person-group><article-title>A first-generation X-inactivation profile of the human X chromosome</article-title><source>Proc Natl Acad Sci USA</source><volume>96</volume><fpage>14440</fpage><lpage>14444</lpage><year>1999</year><pub-id pub-id-type="pmid">10588724</pub-id></element-citation></ref><ref id="R2"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Carrel</surname><given-names>L</given-names></name><name><surname>Willard</surname><given-names>HF</given-names></name></person-group><article-title>X-inactivation profile reveals extensive variability in X-linked gene expression in females</article-title><source>Nature</source><volume>434</volume><fpage>400</fpage><lpage>404</lpage><year>2005</year><pub-id pub-id-type="pmid">15772666</pub-id></element-citation></ref><ref id="R3"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goldberg</surname><given-names>JM</given-names></name><etal></etal></person-group><article-title>Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience</article-title><source>J Clin Oncol</source><volume>21</volume><fpage>3616</fpage><lpage>3622</lpage><year>2003</year><pub-id pub-id-type="pmid">14512392</pub-id></element-citation></ref><ref id="R4"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aifantis</surname><given-names>I</given-names></name><name><surname>Raetz</surname><given-names>E</given-names></name><name><surname>Buonamici</surname><given-names>S</given-names></name></person-group><article-title>Molecular pathogenesis of T-cell leukaemia and lymphoma</article-title><source>Nat Rev Immunol</source><volume>8</volume><fpage>380</fpage><lpage>390</lpage><year>2008</year><pub-id pub-id-type="pmid">18421304</pub-id></element-citation></ref><ref id="R5"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pui</surname><given-names>CH</given-names></name><name><surname>Robison</surname><given-names>LL</given-names></name><name><surname>Look</surname><given-names>AT</given-names></name></person-group><article-title>Acute lymphoblastic leukaemia</article-title><source>Lancet</source><volume>371</volume><fpage>1030</fpage><lpage>1043</lpage><year>2008</year><pub-id pub-id-type="pmid">18358930</pub-id></element-citation></ref><ref id="R6"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gnirke</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing</article-title><source>Nat Biotechnol</source><volume>27</volume><fpage>182</fpage><lpage>189</lpage><year>2009</year><pub-id pub-id-type="pmid">19182786</pub-id></element-citation></ref><ref id="R7"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lower</surname><given-names>KM</given-names></name><etal></etal></person-group><article-title>Mutations in <italic>PHF6</italic> are associated with Borjeson-Forssman-Lehmann syndrome</article-title><source>Nat Genet</source><volume>32</volume><fpage>661</fpage><lpage>665</lpage><year>2002</year><pub-id pub-id-type="pmid">12415272</pub-id></element-citation></ref><ref id="R8"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Borjeson</surname><given-names>M</given-names></name><name><surname>Forssman</surname><given-names>H</given-names></name><name><surname>Lehmann</surname><given-names>O</given-names></name></person-group><article-title>An X-linked, recessively inherited syndrome characterized by grave mental deficiency, epilepsy, and endocrine disorder</article-title><source>Acta Med Scand</source><volume>171</volume><fpage>13</fpage><lpage>21</lpage><year>1962</year><pub-id pub-id-type="pmid">13871358</pub-id></element-citation></ref><ref id="R9"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Turner</surname><given-names>G</given-names></name><etal></etal></person-group><article-title>The clinical picture of the Borjeson-Forssman-Lehmann syndrome in males and heterozygous females with <italic>PHF6</italic> mutations</article-title><source>Clin Genet</source><volume>65</volume><fpage>226</fpage><lpage>232</lpage><year>2004</year><pub-id pub-id-type="pmid">14756673</pub-id></element-citation></ref><ref id="R10"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Baker</surname><given-names>LA</given-names></name><name><surname>Allis</surname><given-names>CD</given-names></name><name><surname>Wang</surname><given-names>GG</given-names></name></person-group><article-title>PHD fingers in human diseases: disorders arising from misinterpreting epigenetic marks</article-title><source>Mutat Res</source><volume>647</volume><fpage>3</fpage><lpage>12</lpage><year>2008</year><pub-id pub-id-type="pmid">18682256</pub-id></element-citation></ref><ref id="R11"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dephoure</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>A quantitative atlas of mitotic phosphorylation</article-title><source>Proc Natl Acad Sci USA</source><volume>105</volume><fpage>10762</fpage><lpage>10767</lpage><year>2008</year><pub-id pub-id-type="pmid">18669648</pub-id></element-citation></ref><ref id="R12"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsuoka</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage</article-title><source>Science</source><volume>316</volume><fpage>1160</fpage><lpage>1166</lpage><year>2007</year><pub-id pub-id-type="pmid">17525332</pub-id></element-citation></ref><ref id="R13"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lowndes</surname><given-names>NF</given-names></name><name><surname>Toh</surname><given-names>GW</given-names></name></person-group><article-title>DNA repair: the importance of phosphorylating histone H2AX</article-title><source>Curr Biol</source><volume>15</volume><fpage>R99</fpage><lpage>R102</lpage><year>2005</year><pub-id pub-id-type="pmid">15694301</pub-id></element-citation></ref><ref id="R14"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Payer</surname><given-names>B</given-names></name><name><surname>Lee</surname><given-names>JT</given-names></name></person-group><article-title>X chromosome dosage compensation: how mammals keep the balance</article-title><source>Annu Rev Genet</source><volume>42</volume><fpage>733</fpage><lpage>772</lpage><year>2008</year><pub-id pub-id-type="pmid">18729722</pub-id></element-citation></ref><ref id="R15"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Carrel</surname><given-names>L</given-names></name><name><surname>Willard</surname><given-names>HF</given-names></name></person-group><article-title>Heterogeneous gene expression from the inactive X chromosome: an X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others</article-title><source>Proc Natl Acad Sci USA</source><volume>96</volume><fpage>7364</fpage><lpage>7369</lpage><year>1999</year><pub-id pub-id-type="pmid">10377420</pub-id></element-citation></ref><ref id="R16"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ferrando</surname><given-names>AA</given-names></name><etal></etal></person-group><article-title>Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia</article-title><source>Cancer Cell</source><volume>1</volume><fpage>75</fpage><lpage>87</lpage><year>2002</year><pub-id pub-id-type="pmid">12086890</pub-id></element-citation></ref><ref id="R17"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Soulier</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL)</article-title><source>Blood</source><volume>106</volume><fpage>274</fpage><lpage>286</lpage><year>2005</year><pub-id pub-id-type="pmid">15774621</pub-id></element-citation></ref><ref id="R18"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Vlierberghe</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia</article-title><source>Blood</source><volume>111</volume><fpage>4668</fpage><lpage>4680</lpage><year>2008</year><pub-id pub-id-type="pmid">18299449</pub-id></element-citation></ref><ref id="R19"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Grotel</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia: a retrospective study of patients treated according to DCOG or COALL protocols</article-title><source>Haematologica</source><volume>91</volume><fpage>1212</fpage><lpage>1221</lpage><year>2006</year><pub-id pub-id-type="pmid">16956820</pub-id></element-citation></ref><ref id="R20"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marks</surname><given-names>DI</given-names></name><etal></etal></person-group><article-title>T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993)</article-title><source>Blood</source><volume>114</volume><fpage>5136</fpage><lpage>5145</lpage><year>2009</year><pub-id pub-id-type="pmid">19828704</pub-id></element-citation></ref><ref id="R21"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rumble</surname><given-names>SM</given-names></name><etal></etal></person-group><article-title>SHRiMP: accurate mapping of short color-space reads</article-title><source>PLoS Comput Biol</source><volume>5</volume><fpage>e1000386</fpage><year>2009</year><pub-id pub-id-type="pmid">19461883</pub-id></element-citation></ref><ref id="R22"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Khiabanian</surname><given-names>H</given-names></name><name><surname>VanVlierberghe</surname><given-names>P</given-names></name><name><surname>Palomero</surname><given-names>T</given-names></name><name><surname>Ferrando</surname><given-names>AA</given-names></name><name><surname>Rabadan</surname><given-names>R</given-names></name></person-group><article-title>ParMap, an algorithm for the identification of complex genomic variations in nextgen sequencing data</article-title><source>Nature Precedings</source><comment>posted online 12 January 2010 (hdl:10101/npre201041451)</comment></element-citation></ref><ref id="R23"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Clappier</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL subtype in very young children</article-title><source>Blood</source><volume>110</volume><fpage>1251</fpage><lpage>1261</lpage><year>2007</year><pub-id pub-id-type="pmid">17452517</pub-id></element-citation></ref><ref id="R24"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Erdogan</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Impact of low copy repeats on the generation of balanced and unbalanced chromosomal aberrations in mental retardation</article-title><source>Cytogenet Genome Res</source><volume>115</volume><fpage>247</fpage><lpage>253</lpage><year>2006</year><pub-id pub-id-type="pmid">17124407</pub-id></element-citation></ref><ref id="R25"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lahortiga</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Duplication of the <italic>MYB</italic> oncogene in T cell acute lymphoblastic leukemia</article-title><source>Nat Genet</source><volume>39</volume><fpage>593</fpage><lpage>595</lpage><year>2007</year><pub-id pub-id-type="pmid">17435759</pub-id></element-citation></ref><ref id="R26"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Voss</surname><given-names>AK</given-names></name><etal></etal></person-group><article-title>Protein and gene expression analysis of <italic>Phf6</italic>, the gene mutated in the Borjeson-Forssman-Lehmann Syndrome of intellectual disability and obesity</article-title><source>Gene Expr Patterns</source><volume>7</volume><fpage>858</fpage><lpage>871</lpage><year>2007</year><pub-id pub-id-type="pmid">17698420</pub-id></element-citation></ref><ref id="R27"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gonzalez-Garcia</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7Rα gene expression in early human thymopoiesis and leukemia</article-title><source>J Exp Med</source><volume>206</volume><fpage>779</fpage><lpage>791</lpage><year>2009</year><pub-id pub-id-type="pmid">19349467</pub-id></element-citation></ref><ref id="R28"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moffat</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen</article-title><source>Cell</source><volume>124</volume><fpage>1283</fpage><lpage>1298</lpage><year>2006</year><pub-id pub-id-type="pmid">16564017</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="F1" position="float"><label>Figure 1</label><caption><p>Next generation sequencing and array CGH analysis of the X chromosome identifies <italic>PHF6</italic> mutations in human T-ALL. (<bold>a</bold>) Overview of mutation screening approach of the human X chromosome exome in a panel of tumor DNA samples from 12 male T-ALL cases using oligonucleotide sequence capture and next generation sequencing with SOLiD3. After filtering and confirmation of high throughput sequencing data, analysis of corresponding remission DNA samples led to the identification of three somatically acquired changes in the <italic>PHF6</italic> gene. (<bold>b</bold>) Schematic overview of the recurrent genomic deletions involving chromosomal band Xq26.3 in 8 human T-ALL samples. Specific genes located in Xq26.3 are shown. (<bold>c</bold>) Detailed view of a representative oligo array-CGH plot of leukemia DNA/control DNA ratios (blue tracing) versus the dye-swap experiment (red tracing) in a patient harboring an Xq26.3 deletion. (<bold>d</bold>) DNA quantitative PCR analysis of <italic>PHF6</italic> copy number dose in female and male reference genomic DNAs and 2 primary samples from male T-ALL cases harboring Xq26.3 deletions.</p></caption><graphic xlink:href="nihms176587f1"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><p><italic>PHF6</italic> mutations and expression in T-ALL lymphoblasts. (<bold>a</bold>) Structure of the PHF6 protein including four nuclear localization signals and two imperfect PHD zinc finger domains. Overview of all <italic>PHF6</italic> mutations identified in primary T-ALL samples and T-ALL cell lines. Filled circles represent nonsense and frameshift mutations, whereas missense mutations are depicted as open circles. Circles filled in gray indicate mutations identified in female T-ALL cases. (<bold>b</bold>) Representative DNA sequencing chromatograms of paired diagnosis and remission genomic T-ALL DNA samples showing a somatic mutation in exon 7 of <italic>PHF6</italic>. (<bold>c</bold>) Western blot analysis of T-ALL cell lines revealed complete loss of PHF6 protein expression in the <italic>PHF6</italic> mutated T-ALL cell lines. (<bold>d</bold>) PHF6 immunostaining in the Jurkat and HPB-ALL, wild-type and mutant T-ALL cell lines, respectively. (<bold>e</bold>) Western blot analysis of PHF6 and gamma-H2AX expression in HEK293T cells upon PHF6 shRNA knockdown. Actin levels are shown as loading control.</p></caption><graphic xlink:href="nihms176587f2"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><p><italic>PHF6</italic> expression in T-ALL lymphoblasts. (<bold>a</bold>) Sequence analysis of paired genomic DNA and cDNA samples shows monoallelic expression of <italic>PHF6</italic> SNP rs17317724 in lymphoblasts from a wild-type <italic>PHF6</italic> female T-ALL case. (<bold>b</bold>) Differential distribution of <italic>PHF6</italic> mutations in T-ALL samples from male and female cases. (<bold>c</bold>) Immunohistochemical analysis of PHF6 expression in wild type and mutant T-ALL lymphoblasts.</p></caption><graphic xlink:href="nihms176587f3"></graphic></fig><fig id="F4" position="float"><label>Figure 4</label><caption><p>Clinical and biological characteristics associated with <italic>PHF6</italic> mutations in T-ALL. (<bold>a</bold>) Frequencies of <italic>PHF6</italic> mutations in pediatric and adult T-ALL samples. (<bold>b</bold>) Differential distribution of <italic>PHF6</italic> mutations in <italic>TLX1/TLX3</italic> positive and negative T-ALL samples. (<bold>c</bold>) Kaplan-Meier curve of overall survival in pediatric T-ALL patients from DCOG trials ALL7, ALL8 and ALL9 with and without <italic>PHF6</italic> mutations. (<bold>d</bold>) Kaplan-Meier survival curve in adult T-ALL patients with and without mutations in <italic>PHF6</italic> treated in ECOG clinical trial ECOG2993.</p></caption><graphic xlink:href="nihms176587f4"></graphic></fig><table-wrap id="T1" position="float" orientation="landscape"><label>Table 1</label><caption><title>Characteristics of 38 primary T-ALL samples showing <italic>PHF6</italic> inactivation</title></caption><table frame="hsides" rules="groups"><thead><tr><th valign="top" align="center" colspan="7" rowspan="1"></th><th colspan="3" valign="top" align="center" rowspan="1"><italic>PHF6</italic> lesion</th></tr><tr><th valign="top" align="center" colspan="7" rowspan="1"></th><th colspan="3" valign="bottom" align="center" rowspan="1"><hr></hr></th></tr><tr><th valign="top" align="center" rowspan="1" colspan="1">ID</th><th valign="top" align="center" rowspan="1" colspan="1">Sex</th><th valign="top" align="center" rowspan="1" colspan="1">Age</th><th valign="top" align="center" rowspan="1" colspan="1">WBC (×10<sup>9</sup>/l)</th><th valign="top" align="center" rowspan="1" colspan="1">Immuno-phenotype</th><th valign="top" align="center" rowspan="1" colspan="1">Genetic subtype</th><th valign="top" align="center" rowspan="1" colspan="1"><italic>NOTCH1</italic></th><th valign="top" align="center" rowspan="1" colspan="1">Type of alteration</th><th valign="top" align="center" rowspan="1" colspan="1">Predicted protein</th><th valign="top" align="center" rowspan="1" colspan="1">Germline/somatic</th></tr></thead><tbody><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td colspan="9" align="left" valign="top" rowspan="1"><italic>PHF6</italic> deletions</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td colspan="9" align="center" valign="bottom" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">77</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Deletion (0.55 Mb)</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">46</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Deletion (0.23 Mb)</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">3</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">31</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Deletion (1.50 Mb)</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">4</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1">unknown</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Deletion (0.27 Mb)</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">5</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>HOXA</italic></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Deletion (1.90 Mb)</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">6</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1">unknown</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Deletion (0.20 Mb)</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">7</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Deletion (0.08 Mb)</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">8</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1">Unkn</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Deletion (0.11 Mb)</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td colspan="9" align="center" valign="bottom" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td colspan="9" align="left" valign="top" rowspan="1"><italic>PHF6</italic> mutations</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td colspan="9" align="center" valign="bottom" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">9</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">185</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.G122X</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">10</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">417</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.R116X</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">11</td><td align="center" valign="top" rowspan="1" colspan="1">F</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">280</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.F172fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">12</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">405</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.Y303fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">13</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">159</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.K235X</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">14</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">500</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.A41fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">15</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">347</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>HOXA</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.K274X</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">16</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">129</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1">unknown</td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.D333fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">17</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">174</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.R225X</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">18</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">27</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.R116X</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">19</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">310</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TAL1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.C283R</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">20</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">189</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TAL1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.C28fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">21</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">170</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.H44fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">22</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">21</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.H43fs</td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">22</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">21</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.H43fs</td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">23</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.T98fs</td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">24</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">14</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.Y105fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">25</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">28</td><td align="center" valign="top" rowspan="1" colspan="1">Mature</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.S158fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">26</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.C215Y</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">27</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-T</td><td align="center" valign="top" rowspan="1" colspan="1">Unkn</td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.C215F</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">28</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">31</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1">Unkn</td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.C215Y</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">29</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Mature</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX3</italic></td><td align="center" valign="top" rowspan="1" colspan="1">mut</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.T300A</td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">30</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">21</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.A311P</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">31</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">30</td><td align="center" valign="top" rowspan="1" colspan="1">Mature</td><td align="center" valign="top" rowspan="1" colspan="1">Unkn</td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.C280Y</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">32</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">23</td><td align="center" valign="top" rowspan="1" colspan="1">Cortical</td><td align="center" valign="top" rowspan="1" colspan="1">Unkn</td><td align="center" valign="top" rowspan="1" colspan="1">wt</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.H329R</td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">33</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TAL1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.R257X</td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">34</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Ped</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.S191fs</td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">35</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Missense</td><td align="center" valign="top" rowspan="1" colspan="1">p.C215F</td><td align="center" valign="top" rowspan="1" colspan="1">Somatic</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">36</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>TLX1</italic></td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.Y303X</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">37</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Unkn</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Nonsense</td><td align="center" valign="top" rowspan="1" colspan="1">p.R274X</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">38</td><td align="center" valign="top" rowspan="1" colspan="1">M</td><td align="center" valign="top" rowspan="1" colspan="1">Adult</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Unkn</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td><td align="center" valign="top" rowspan="1" colspan="1">Frameshift</td><td align="center" valign="top" rowspan="1" colspan="1">p.H135fs</td><td align="center" valign="top" rowspan="1" colspan="1">NA</td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p>Ped, pediatric; NA, not available; mut, mutated; wt, 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