LymphedemaV1, Pmc, Corpus, bibRecord, 002E24

Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival

Identifieur interne : 002E24 ( Pmc/Corpus ); précédent : 002E23; suivant : 002E25

Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival

Auteurs : Csaba Bödör ; Aline Renneville ; Matthew Smith ; Aurélie Charazac ; Sameena Iqbal ; Pascaline Étancelin ; Jamie Cavenagh ; Michael J. Barnett ; Karolina Kramarzová ; Biju Krishnan ; András Matolcsy ; Claude Preudhomme ; Jude Fitzgibbon ; Carolyn Owen

Source :

Haematologica [ 0390-6078 ] ; 2012.

RBID : PMC:3366655

Abstract

While most myelodysplastic syndrome/acute myeloid leukemia cases are sporadic, rare familial cases occur and provide some insight into leukemogenesis. The most clearly defined familial cases result from inherited mutations in RUNX1 or CEBPA. Recently, novel germline mutations in GATA2 have been reported. We, therefore, investigated individuals from families with one or more first-degree relatives with myelodysplastic syndrome/acute myeloid leukemia with wild-type RUNX1 and CEBPA, for GATA2 mutations. Screening for other recurrent mutations was also performed. A GATA2 p.Thr354Met mutation was observed in a pedigree in which 2 first-degree cousins developed high-risk myelodys-plastic syndrome with monosomy 7. They were also observed to have acquired identical somatic ASXL1 mutations and both died despite stem cell transplantation. These findings confirm that germline GATA2 mutations predispose to familial myelodysplastic syndrome/acute myeloid leukemia, and that monosomy 7 and ASXL1 mutations may be recurrent secondary genetic abnormalities triggering overt malignancy in these families.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366655

DOI: 10.3324/haematol.2011.054361
PubMed: 22271902
PubMed Central: 3366655

Links to Exploration step

PMC:3366655

Le document en format XML

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 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and <italic>ASXL1</italic>
 mutation demonstrating rapid onset and poor survival</title>
<author><name sortKey="Bodor, Csaba" sort="Bodor, Csaba" uniqKey="Bodor C" first="Csaba" last="Bödör">Csaba Bödör</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="af2-0970890">1<sup>st</sup>
 Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Renneville, Aline" sort="Renneville, Aline" uniqKey="Renneville A" first="Aline" last="Renneville">Aline Renneville</name>
<affiliation><nlm:aff id="af3-0970890">Centre de Biologie-Pathologie, Laboratoire d’Hématologie, CHRU de Lille, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Matthew" sort="Smith, Matthew" uniqKey="Smith M" first="Matthew" last="Smith">Matthew Smith</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Charazac, Aurelie" sort="Charazac, Aurelie" uniqKey="Charazac A" first="Aurélie" last="Charazac">Aurélie Charazac</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Iqbal, Sameena" sort="Iqbal, Sameena" uniqKey="Iqbal S" first="Sameena" last="Iqbal">Sameena Iqbal</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Etancelin, Pascaline" sort="Etancelin, Pascaline" uniqKey="Etancelin P" first="Pascaline" last="Étancelin">Pascaline Étancelin</name>
<affiliation><nlm:aff id="af3-0970890">Centre de Biologie-Pathologie, Laboratoire d’Hématologie, CHRU de Lille, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cavenagh, Jamie" sort="Cavenagh, Jamie" uniqKey="Cavenagh J" first="Jamie" last="Cavenagh">Jamie Cavenagh</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Barnett, Michael J" sort="Barnett, Michael J" uniqKey="Barnett M" first="Michael J" last="Barnett">Michael J. Barnett</name>
<affiliation><nlm:aff id="af4-0970890">Leukemia/BMT Program of British Columbia, British Columbia Cancer Agency and Vancouver General Hospital, and University of British Columbia, Vancouver, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kramarzova, Karolina" sort="Kramarzova, Karolina" uniqKey="Kramarzova K" first="Karolina" last="Kramarzová">Karolina Kramarzová</name>
<affiliation><nlm:aff id="af5-0970890">Department of Pediatric Hematology and Oncology, 2<sup>nd</sup>
 School of Medicine, Charles University, Prague, Czech Republic</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Krishnan, Biju" sort="Krishnan, Biju" uniqKey="Krishnan B" first="Biju" last="Krishnan">Biju Krishnan</name>
<affiliation><nlm:aff id="af6-0970890">Department of Haematology, Queens Hospital, Essex, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matolcsy, Andras" sort="Matolcsy, Andras" uniqKey="Matolcsy A" first="András" last="Matolcsy">András Matolcsy</name>
<affiliation><nlm:aff id="af2-0970890">1<sup>st</sup>
 Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Preudhomme, Claude" sort="Preudhomme, Claude" uniqKey="Preudhomme C" first="Claude" last="Preudhomme">Claude Preudhomme</name>
<affiliation><nlm:aff id="af3-0970890">Centre de Biologie-Pathologie, Laboratoire d’Hématologie, CHRU de Lille, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fitzgibbon, Jude" sort="Fitzgibbon, Jude" uniqKey="Fitzgibbon J" first="Jude" last="Fitzgibbon">Jude Fitzgibbon</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Owen, Carolyn" sort="Owen, Carolyn" uniqKey="Owen C" first="Carolyn" last="Owen">Carolyn Owen</name>
<affiliation><nlm:aff id="af7-0970890">Division of Hematology & Hematological Malignancies, University of Calgary, Calgary, Canada</nlm:aff>
</affiliation>
</author>
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<date when="2012">2012</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Germ-line <italic>GATA2</italic>
 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and <italic>ASXL1</italic>
 mutation demonstrating rapid onset and poor survival</title>
<author><name sortKey="Bodor, Csaba" sort="Bodor, Csaba" uniqKey="Bodor C" first="Csaba" last="Bödör">Csaba Bödör</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="af2-0970890">1<sup>st</sup>
 Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Renneville, Aline" sort="Renneville, Aline" uniqKey="Renneville A" first="Aline" last="Renneville">Aline Renneville</name>
<affiliation><nlm:aff id="af3-0970890">Centre de Biologie-Pathologie, Laboratoire d’Hématologie, CHRU de Lille, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Matthew" sort="Smith, Matthew" uniqKey="Smith M" first="Matthew" last="Smith">Matthew Smith</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Charazac, Aurelie" sort="Charazac, Aurelie" uniqKey="Charazac A" first="Aurélie" last="Charazac">Aurélie Charazac</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Iqbal, Sameena" sort="Iqbal, Sameena" uniqKey="Iqbal S" first="Sameena" last="Iqbal">Sameena Iqbal</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Etancelin, Pascaline" sort="Etancelin, Pascaline" uniqKey="Etancelin P" first="Pascaline" last="Étancelin">Pascaline Étancelin</name>
<affiliation><nlm:aff id="af3-0970890">Centre de Biologie-Pathologie, Laboratoire d’Hématologie, CHRU de Lille, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cavenagh, Jamie" sort="Cavenagh, Jamie" uniqKey="Cavenagh J" first="Jamie" last="Cavenagh">Jamie Cavenagh</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Barnett, Michael J" sort="Barnett, Michael J" uniqKey="Barnett M" first="Michael J" last="Barnett">Michael J. Barnett</name>
<affiliation><nlm:aff id="af4-0970890">Leukemia/BMT Program of British Columbia, British Columbia Cancer Agency and Vancouver General Hospital, and University of British Columbia, Vancouver, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kramarzova, Karolina" sort="Kramarzova, Karolina" uniqKey="Kramarzova K" first="Karolina" last="Kramarzová">Karolina Kramarzová</name>
<affiliation><nlm:aff id="af5-0970890">Department of Pediatric Hematology and Oncology, 2<sup>nd</sup>
 School of Medicine, Charles University, Prague, Czech Republic</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Krishnan, Biju" sort="Krishnan, Biju" uniqKey="Krishnan B" first="Biju" last="Krishnan">Biju Krishnan</name>
<affiliation><nlm:aff id="af6-0970890">Department of Haematology, Queens Hospital, Essex, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matolcsy, Andras" sort="Matolcsy, Andras" uniqKey="Matolcsy A" first="András" last="Matolcsy">András Matolcsy</name>
<affiliation><nlm:aff id="af2-0970890">1<sup>st</sup>
 Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Preudhomme, Claude" sort="Preudhomme, Claude" uniqKey="Preudhomme C" first="Claude" last="Preudhomme">Claude Preudhomme</name>
<affiliation><nlm:aff id="af3-0970890">Centre de Biologie-Pathologie, Laboratoire d’Hématologie, CHRU de Lille, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fitzgibbon, Jude" sort="Fitzgibbon, Jude" uniqKey="Fitzgibbon J" first="Jude" last="Fitzgibbon">Jude Fitzgibbon</name>
<affiliation><nlm:aff id="af1-0970890">Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Owen, Carolyn" sort="Owen, Carolyn" uniqKey="Owen C" first="Carolyn" last="Owen">Carolyn Owen</name>
<affiliation><nlm:aff id="af7-0970890">Division of Hematology & Hematological Malignancies, University of Calgary, Calgary, Canada</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Haematologica</title>
<idno type="ISSN">0390-6078</idno>
<idno type="eISSN">1592-8721</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>While most myelodysplastic syndrome/acute myeloid leukemia cases are sporadic, rare familial cases occur and provide some insight into leukemogenesis. The most clearly defined familial cases result from inherited mutations in <italic>RUNX1</italic>
 or <italic>CEBPA</italic>
. Recently, novel germline mutations in <italic>GATA2</italic>
 have been reported. We, therefore, investigated individuals from families with one or more first-degree relatives with myelodysplastic syndrome/acute myeloid leukemia with wild-type <italic>RUNX1</italic>
 and <italic>CEBPA</italic>
, for <italic>GATA2</italic>
 mutations. Screening for other recurrent mutations was also performed. A <italic>GATA2</italic>
 p.Thr354Met mutation was observed in a pedigree in which 2 first-degree cousins developed high-risk myelodys-plastic syndrome with monosomy 7. They were also observed to have acquired identical somatic <italic>ASXL1</italic>
 mutations and both died despite stem cell transplantation. These findings confirm that germline <italic>GATA2</italic>
 mutations predispose to familial myelodysplastic syndrome/acute myeloid leukemia, and that monosomy 7 and <italic>ASXL1</italic>
 mutations may be recurrent secondary genetic abnormalities triggering overt malignancy in these families.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">Haematologica</journal-id>
<journal-id journal-id-type="iso-abbrev">Haematologica</journal-id>
<journal-id journal-id-type="hwp">haematol</journal-id>
<journal-id journal-id-type="publisher-id">Haematologica</journal-id>
<journal-title-group><journal-title>Haematologica</journal-title>
</journal-title-group>
<issn pub-type="ppub">0390-6078</issn>
<issn pub-type="epub">1592-8721</issn>
<publisher><publisher-name>Ferrata Storti Foundation</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22271902</article-id>
<article-id pub-id-type="pmc">3366655</article-id>
<article-id pub-id-type="doi">10.3324/haematol.2011.054361</article-id>
<article-id pub-id-type="publisher-id">0970890</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Articles and Brief Reports</subject>
<subj-group><subject>Myelodysplastic Syndromes</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Germ-line <italic>GATA2</italic>
 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and <italic>ASXL1</italic>
 mutation demonstrating rapid onset and poor survival</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Bödör</surname>
<given-names>Csaba</given-names>
</name>
<xref ref-type="aff" rid="af1-0970890">1</xref>
<xref ref-type="aff" rid="af2-0970890">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Renneville</surname>
<given-names>Aline</given-names>
</name>
<xref ref-type="aff" rid="af3-0970890">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Smith</surname>
<given-names>Matthew</given-names>
</name>
<xref ref-type="aff" rid="af1-0970890">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Charazac</surname>
<given-names>Aurélie</given-names>
</name>
<xref ref-type="aff" rid="af1-0970890">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Iqbal</surname>
<given-names>Sameena</given-names>
</name>
<xref ref-type="aff" rid="af1-0970890">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Étancelin</surname>
<given-names>Pascaline</given-names>
</name>
<xref ref-type="aff" rid="af3-0970890">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cavenagh</surname>
<given-names>Jamie</given-names>
</name>
<xref ref-type="aff" rid="af1-0970890">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Barnett</surname>
<given-names>Michael J</given-names>
</name>
<xref ref-type="aff" rid="af4-0970890">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kramarzová</surname>
<given-names>Karolina</given-names>
</name>
<xref ref-type="aff" rid="af5-0970890">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Krishnan</surname>
<given-names>Biju</given-names>
</name>
<xref ref-type="aff" rid="af6-0970890">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matolcsy</surname>
<given-names>András</given-names>
</name>
<xref ref-type="aff" rid="af2-0970890">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Preudhomme</surname>
<given-names>Claude</given-names>
</name>
<xref ref-type="aff" rid="af3-0970890">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fitzgibbon</surname>
<given-names>Jude</given-names>
</name>
<xref ref-type="aff" rid="af1-0970890">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Owen</surname>
<given-names>Carolyn</given-names>
</name>
<xref ref-type="aff" rid="af7-0970890">7</xref>
<xref ref-type="corresp" rid="c1-0970890"></xref>
</contrib>
</contrib-group>
<aff id="af1-0970890"><label>1</label>
Centre of Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK</aff>
<aff id="af2-0970890"><label>2</label>
1<sup>st</sup>
 Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary</aff>
<aff id="af3-0970890"><label>3</label>
Centre de Biologie-Pathologie, Laboratoire d’Hématologie, CHRU de Lille, France</aff>
<aff id="af4-0970890"><label>4</label>
Leukemia/BMT Program of British Columbia, British Columbia Cancer Agency and Vancouver General Hospital, and University of British Columbia, Vancouver, Canada</aff>
<aff id="af5-0970890"><label>5</label>
Department of Pediatric Hematology and Oncology, 2<sup>nd</sup>
 School of Medicine, Charles University, Prague, Czech Republic</aff>
<aff id="af6-0970890"><label>6</label>
Department of Haematology, Queens Hospital, Essex, UK</aff>
<aff id="af7-0970890"><label>7</label>
Division of Hematology & Hematological Malignancies, University of Calgary, Calgary, Canada</aff>
<author-notes><corresp id="c1-0970890">Correspondence: Carolyn Owen, 603 South Tower, Foothills Medical Centre, 1403-29th St NW, Calgary, AB, Canada, T2N 2T9. Phone: international +1.403.9443265. Fax: international +1.403.9448352. E-mail: <email>carolyn.owen@albertahealthservices.ca</email>
 or Jude Fitzgibbon, Centre of Haemato-Oncology, Barts Cancer Institute, Charterhouse Square, London, EC1M 6BQ, UK. Phone: international +44.20.78823804. Fax: international +44.20.7882 3891. E-mail: <email>j.fitzgibbon@qmul.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>6</month>
<year>2012</year>
</pub-date>
<volume>97</volume>
<issue>6</issue>
<fpage>890</fpage>
<lpage>894</lpage>
<history><date date-type="received"><day>01</day>
<month>9</month>
<year>2011</year>
</date>
<date date-type="rev-recd"><day>19</day>
<month>12</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>23</day>
<month>12</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright© Ferrata Storti Foundation</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<self-uri content-type="pdf" xlink:type="simple" xlink:href="97890.pdf"></self-uri>
<abstract><p>While most myelodysplastic syndrome/acute myeloid leukemia cases are sporadic, rare familial cases occur and provide some insight into leukemogenesis. The most clearly defined familial cases result from inherited mutations in <italic>RUNX1</italic>
 or <italic>CEBPA</italic>
. Recently, novel germline mutations in <italic>GATA2</italic>
 have been reported. We, therefore, investigated individuals from families with one or more first-degree relatives with myelodysplastic syndrome/acute myeloid leukemia with wild-type <italic>RUNX1</italic>
 and <italic>CEBPA</italic>
, for <italic>GATA2</italic>
 mutations. Screening for other recurrent mutations was also performed. A <italic>GATA2</italic>
 p.Thr354Met mutation was observed in a pedigree in which 2 first-degree cousins developed high-risk myelodys-plastic syndrome with monosomy 7. They were also observed to have acquired identical somatic <italic>ASXL1</italic>
 mutations and both died despite stem cell transplantation. These findings confirm that germline <italic>GATA2</italic>
 mutations predispose to familial myelodysplastic syndrome/acute myeloid leukemia, and that monosomy 7 and <italic>ASXL1</italic>
 mutations may be recurrent secondary genetic abnormalities triggering overt malignancy in these families.</p>
</abstract>
<kwd-group><kwd>familial</kwd>
<kwd>myelodysplastic syndromes</kwd>
<kwd>GATA2</kwd>
<kwd>monosomy 7</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival

Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival

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