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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Secondary Somatic Mutations Restoring <italic>RAD51C</italic>
and <italic>RAD51D</italic>
Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma</title>
<author><name sortKey="Kondrashova, Olga" sort="Kondrashova, Olga" uniqKey="Kondrashova O" first="Olga" last="Kondrashova">Olga Kondrashova</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nguyen, Minh" sort="Nguyen, Minh" uniqKey="Nguyen M" first="Minh" last="Nguyen">Minh Nguyen</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shield Artin, Kristy" sort="Shield Artin, Kristy" uniqKey="Shield Artin K" first="Kristy" last="Shield-Artin">Kristy Shield-Artin</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V." last="Tinker">Anna V. Tinker</name>
<affiliation><nlm:aff id="A4">British Columbia Cancer Agency, Vancouver, British Columbia, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Teng, Nelson N H" sort="Teng, Nelson N H" uniqKey="Teng N" first="Nelson N. H." last="Teng">Nelson N. H. Teng</name>
<affiliation><nlm:aff id="A5">Stanford University, Palo Alto, California</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harrell, Maria I" sort="Harrell, Maria I" uniqKey="Harrell M" first="Maria I." last="Harrell">Maria I. Harrell</name>
<affiliation><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuiper, Michael J" sort="Kuiper, Michael J" uniqKey="Kuiper M" first="Michael J." last="Kuiper">Michael J. Kuiper</name>
<affiliation><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ho, Gwo Yaw" sort="Ho, Gwo Yaw" uniqKey="Ho G" first="Gwo-Yaw" last="Ho">Gwo-Yaw Ho</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jasin, Maria" sort="Jasin, Maria" uniqKey="Jasin M" first="Maria" last="Jasin">Maria Jasin</name>
<affiliation><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Prakash, Rohit" sort="Prakash, Rohit" uniqKey="Prakash R" first="Rohit" last="Prakash">Rohit Prakash</name>
<affiliation><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kass, Elizabeth M" sort="Kass, Elizabeth M" uniqKey="Kass E" first="Elizabeth M." last="Kass">Elizabeth M. Kass</name>
<affiliation><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sullivan, Meghan R" sort="Sullivan, Meghan R" uniqKey="Sullivan M" first="Meghan R." last="Sullivan">Meghan R. Sullivan</name>
<affiliation><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brunette, Gregory J" sort="Brunette, Gregory J" uniqKey="Brunette G" first="Gregory J." last="Brunette">Gregory J. Brunette</name>
<affiliation><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bernstein, Kara A" sort="Bernstein, Kara A" uniqKey="Bernstein K" first="Kara A." last="Bernstein">Kara A. Bernstein</name>
<affiliation><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L." last="Coleman">Robert L. Coleman</name>
<affiliation><nlm:aff id="A11">The University of Texas MD Anderson Cancer Center, Houston, Texas</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
<affiliation><nlm:aff id="A12">Institut Bergonié, Bordeaux, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Friedlander, Michael" sort="Friedlander, Michael" uniqKey="Friedlander M" first="Michael" last="Friedlander">Michael Friedlander</name>
<affiliation><nlm:aff id="A13">University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kichenadasse, Ganessan" sort="Kichenadasse, Ganessan" uniqKey="Kichenadasse G" first="Ganessan" last="Kichenadasse">Ganessan Kichenadasse</name>
<affiliation><nlm:aff id="A14">Flinders University, Adelaide, South Australia, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="O Malley, David M" sort="O Malley, David M" uniqKey="O Malley D" first="David M." last="O'Malley">David M. O'Malley</name>
<affiliation><nlm:aff id="A15">The Ohio State University, James Cancer Center, Columbus, Ohio</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oza, Amit" sort="Oza, Amit" uniqKey="Oza A" first="Amit" last="Oza">Amit Oza</name>
<affiliation><nlm:aff id="A16">Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<affiliation><nlm:aff id="A17">Foundation Medicine, Inc., Cambridge, Massachusetts</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Robillard, Liliane" sort="Robillard, Liliane" uniqKey="Robillard L" first="Liliane" last="Robillard">Liliane Robillard</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wakefield, Matthew J" sort="Wakefield, Matthew J" uniqKey="Wakefield M" first="Matthew J." last="Wakefield">Matthew J. Wakefield</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kaufmann, Scott H" sort="Kaufmann, Scott H" uniqKey="Kaufmann S" first="Scott H." last="Kaufmann">Scott H. Kaufmann</name>
<affiliation><nlm:aff id="A21">Mayo Clinic Cancer Center, Rochester, Minnesota</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Simmons, Andrew D" sort="Simmons, Andrew D" uniqKey="Simmons A" first="Andrew D." last="Simmons">Andrew D. Simmons</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harding, Thomas C" sort="Harding, Thomas C" uniqKey="Harding T" first="Thomas C." last="Harding">Thomas C. Harding</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A." last="Mcneish">Iain A. Mcneish</name>
<affiliation><nlm:aff id="A22">Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Swisher, Elizabeth M" sort="Swisher, Elizabeth M" uniqKey="Swisher E" first="Elizabeth M." last="Swisher">Elizabeth M. Swisher</name>
<affiliation><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lin, Kevin K" sort="Lin, Kevin K" uniqKey="Lin K" first="Kevin K." last="Lin">Kevin K. Lin</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L." last="Scott">Clare L. Scott</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">28588062</idno>
<idno type="pmc">5612362</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612362</idno>
<idno type="RBID">PMC:5612362</idno>
<idno type="doi">10.1158/2159-8290.CD-17-0419</idno>
<date when="2017">2017</date>
<idno type="wicri:Area/Pmc/Corpus">001E77</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E77</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Secondary Somatic Mutations Restoring <italic>RAD51C</italic>
and <italic>RAD51D</italic>
Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma</title>
<author><name sortKey="Kondrashova, Olga" sort="Kondrashova, Olga" uniqKey="Kondrashova O" first="Olga" last="Kondrashova">Olga Kondrashova</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nguyen, Minh" sort="Nguyen, Minh" uniqKey="Nguyen M" first="Minh" last="Nguyen">Minh Nguyen</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shield Artin, Kristy" sort="Shield Artin, Kristy" uniqKey="Shield Artin K" first="Kristy" last="Shield-Artin">Kristy Shield-Artin</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V." last="Tinker">Anna V. Tinker</name>
<affiliation><nlm:aff id="A4">British Columbia Cancer Agency, Vancouver, British Columbia, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Teng, Nelson N H" sort="Teng, Nelson N H" uniqKey="Teng N" first="Nelson N. H." last="Teng">Nelson N. H. Teng</name>
<affiliation><nlm:aff id="A5">Stanford University, Palo Alto, California</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harrell, Maria I" sort="Harrell, Maria I" uniqKey="Harrell M" first="Maria I." last="Harrell">Maria I. Harrell</name>
<affiliation><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuiper, Michael J" sort="Kuiper, Michael J" uniqKey="Kuiper M" first="Michael J." last="Kuiper">Michael J. Kuiper</name>
<affiliation><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ho, Gwo Yaw" sort="Ho, Gwo Yaw" uniqKey="Ho G" first="Gwo-Yaw" last="Ho">Gwo-Yaw Ho</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jasin, Maria" sort="Jasin, Maria" uniqKey="Jasin M" first="Maria" last="Jasin">Maria Jasin</name>
<affiliation><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Prakash, Rohit" sort="Prakash, Rohit" uniqKey="Prakash R" first="Rohit" last="Prakash">Rohit Prakash</name>
<affiliation><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kass, Elizabeth M" sort="Kass, Elizabeth M" uniqKey="Kass E" first="Elizabeth M." last="Kass">Elizabeth M. Kass</name>
<affiliation><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sullivan, Meghan R" sort="Sullivan, Meghan R" uniqKey="Sullivan M" first="Meghan R." last="Sullivan">Meghan R. Sullivan</name>
<affiliation><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brunette, Gregory J" sort="Brunette, Gregory J" uniqKey="Brunette G" first="Gregory J." last="Brunette">Gregory J. Brunette</name>
<affiliation><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bernstein, Kara A" sort="Bernstein, Kara A" uniqKey="Bernstein K" first="Kara A." last="Bernstein">Kara A. Bernstein</name>
<affiliation><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L." last="Coleman">Robert L. Coleman</name>
<affiliation><nlm:aff id="A11">The University of Texas MD Anderson Cancer Center, Houston, Texas</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
<affiliation><nlm:aff id="A12">Institut Bergonié, Bordeaux, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Friedlander, Michael" sort="Friedlander, Michael" uniqKey="Friedlander M" first="Michael" last="Friedlander">Michael Friedlander</name>
<affiliation><nlm:aff id="A13">University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kichenadasse, Ganessan" sort="Kichenadasse, Ganessan" uniqKey="Kichenadasse G" first="Ganessan" last="Kichenadasse">Ganessan Kichenadasse</name>
<affiliation><nlm:aff id="A14">Flinders University, Adelaide, South Australia, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="O Malley, David M" sort="O Malley, David M" uniqKey="O Malley D" first="David M." last="O'Malley">David M. O'Malley</name>
<affiliation><nlm:aff id="A15">The Ohio State University, James Cancer Center, Columbus, Ohio</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oza, Amit" sort="Oza, Amit" uniqKey="Oza A" first="Amit" last="Oza">Amit Oza</name>
<affiliation><nlm:aff id="A16">Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<affiliation><nlm:aff id="A17">Foundation Medicine, Inc., Cambridge, Massachusetts</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Robillard, Liliane" sort="Robillard, Liliane" uniqKey="Robillard L" first="Liliane" last="Robillard">Liliane Robillard</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wakefield, Matthew J" sort="Wakefield, Matthew J" uniqKey="Wakefield M" first="Matthew J." last="Wakefield">Matthew J. Wakefield</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kaufmann, Scott H" sort="Kaufmann, Scott H" uniqKey="Kaufmann S" first="Scott H." last="Kaufmann">Scott H. Kaufmann</name>
<affiliation><nlm:aff id="A21">Mayo Clinic Cancer Center, Rochester, Minnesota</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Simmons, Andrew D" sort="Simmons, Andrew D" uniqKey="Simmons A" first="Andrew D." last="Simmons">Andrew D. Simmons</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harding, Thomas C" sort="Harding, Thomas C" uniqKey="Harding T" first="Thomas C." last="Harding">Thomas C. Harding</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A." last="Mcneish">Iain A. Mcneish</name>
<affiliation><nlm:aff id="A22">Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Swisher, Elizabeth M" sort="Swisher, Elizabeth M" uniqKey="Swisher E" first="Elizabeth M." last="Swisher">Elizabeth M. Swisher</name>
<affiliation><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lin, Kevin K" sort="Lin, Kevin K" uniqKey="Lin K" first="Kevin K." last="Lin">Kevin K. Lin</name>
<affiliation><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L." last="Scott">Clare L. Scott</name>
<affiliation><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Cancer discovery</title>
<idno type="ISSN">2159-8274</idno>
<idno type="eISSN">2159-8290</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">High-grade epithelial ovarian carcinomas containing mutated <italic>BRCA1</italic>
or <italic>BRCA2</italic>
(<italic>BRCA1/2</italic>
) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and PARP inhibitors (PARPi), while restoration of HR function due to secondary mutations in <italic>BRCA1/2</italic>
has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pretreatment and postprogression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase II study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed ovarian carcinoma. In 6 of 12 pretreatment biopsies, a truncation mutation in <italic>BRCA1, RAD51C,</italic>
or <italic>RAD51D</italic>
was identified. In five of six paired postprogression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for <italic>RAD51C</italic>
. <italic>In vitro</italic>
complementation assays and a patient-derived xenograft, as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations.</p>
<sec id="S1"><title>Significance</title>
<p id="P2">Analyses of primary and secondary mutations in <italic>RAD51C</italic>
and <italic>RAD51D</italic>
provide evidence for these primary mutations in conferring PARPi sensitivity and secondary mutations as a mechanism of acquired PARPi resistance. PARPi resistance due to secondary mutations underpins the need for early delivery of PARPi therapy and for combination strategies.</p>
</sec>
</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>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101561693</journal-id>
<journal-id journal-id-type="pubmed-jr-id">39259</journal-id>
<journal-id journal-id-type="nlm-ta">Cancer Discov</journal-id>
<journal-id journal-id-type="iso-abbrev">Cancer Discov</journal-id>
<journal-title-group><journal-title>Cancer discovery</journal-title>
</journal-title-group>
<issn pub-type="ppub">2159-8274</issn>
<issn pub-type="epub">2159-8290</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">28588062</article-id>
<article-id pub-id-type="pmc">5612362</article-id>
<article-id pub-id-type="doi">10.1158/2159-8290.CD-17-0419</article-id>
<article-id pub-id-type="manuscript">NIHMS904258</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Secondary Somatic Mutations Restoring <italic>RAD51C</italic>
and <italic>RAD51D</italic>
Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kondrashova</surname>
<given-names>Olga</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nguyen</surname>
<given-names>Minh</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shield-Artin</surname>
<given-names>Kristy</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tinker</surname>
<given-names>Anna V.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Teng</surname>
<given-names>Nelson N.H.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harrell</surname>
<given-names>Maria I.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kuiper</surname>
<given-names>Michael J.</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ho</surname>
<given-names>Gwo-Yaw</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Barker</surname>
<given-names>Holly</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jasin</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Prakash</surname>
<given-names>Rohit</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kass</surname>
<given-names>Elizabeth M.</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sullivan</surname>
<given-names>Meghan R.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brunette</surname>
<given-names>Gregory J.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bernstein</surname>
<given-names>Kara A.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Coleman</surname>
<given-names>Robert L.</given-names>
</name>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Floquet</surname>
<given-names>Anne</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Friedlander</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kichenadasse</surname>
<given-names>Ganessan</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>O'Malley</surname>
<given-names>David M.</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Oza</surname>
<given-names>Amit</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sun</surname>
<given-names>James</given-names>
</name>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Robillard</surname>
<given-names>Liliane</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Maloney</surname>
<given-names>Lara</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><collab>David Bowtell on behalf of the AOCS Study Group</collab>
<xref ref-type="aff" rid="A18">18</xref>
<xref ref-type="aff" rid="A19">19</xref>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Giordano</surname>
<given-names>Heidi</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wakefield</surname>
<given-names>Matthew J.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kaufmann</surname>
<given-names>Scott H.</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Simmons</surname>
<given-names>Andrew D.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harding</surname>
<given-names>Thomas C.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Raponi</surname>
<given-names>Mitch</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McNeish</surname>
<given-names>Iain A.</given-names>
</name>
<xref ref-type="aff" rid="A22">22</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Swisher</surname>
<given-names>Elizabeth M.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lin</surname>
<given-names>Kevin K.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Scott</surname>
<given-names>Clare L.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</aff>
<aff id="A2"><label>2</label>
Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</aff>
<aff id="A3"><label>3</label>
Clovis Oncology, Inc., Boulder, Colorado</aff>
<aff id="A4"><label>4</label>
British Columbia Cancer Agency, Vancouver, British Columbia, Canada</aff>
<aff id="A5"><label>5</label>
Stanford University, Palo Alto, California</aff>
<aff id="A6"><label>6</label>
University of Washington, Seattle, Washington</aff>
<aff id="A7"><label>7</label>
Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</aff>
<aff id="A8"><label>8</label>
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</aff>
<aff id="A9"><label>9</label>
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</aff>
<aff id="A10"><label>10</label>
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</aff>
<aff id="A11"><label>11</label>
The University of Texas MD Anderson Cancer Center, Houston, Texas</aff>
<aff id="A12"><label>12</label>
Institut Bergonié, Bordeaux, France</aff>
<aff id="A13"><label>13</label>
University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales, Australia</aff>
<aff id="A14"><label>14</label>
Flinders University, Adelaide, South Australia, Australia</aff>
<aff id="A15"><label>15</label>
The Ohio State University, James Cancer Center, Columbus, Ohio</aff>
<aff id="A16"><label>16</label>
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada</aff>
<aff id="A17"><label>17</label>
Foundation Medicine, Inc., Cambridge, Massachusetts</aff>
<aff id="A18"><label>18</label>
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</aff>
<aff id="A19"><label>19</label>
Centre for Cancer Research, University of Sydney at Westmead Millennium Institute, and Departments of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia</aff>
<aff id="A20"><label>20</label>
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</aff>
<aff id="A21"><label>21</label>
Mayo Clinic Cancer Center, Rochester, Minnesota</aff>
<aff id="A22"><label>22</label>
Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom</aff>
<author-notes><corresp id="FN1">Corresponding Author: Clare L. Scott, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia. Phone: 61-3-9345-2498; Fax: 61-3-9347-0852; <email>scottc@wehi.edu.au</email>
</corresp>
<fn id="FN2" fn-type="equal"><p>O. Kondrashova, M. Nguyen, K. Shield-Artin, K.K. Lin, and Clare L. Scott contributed equally to this article.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>7</day>
<month>9</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub"><day>06</day>
<month>6</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="ppub"><month>9</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>25</day>
<month>9</month>
<year>2017</year>
</pub-date>
<volume>7</volume>
<issue>9</issue>
<fpage>984</fpage>
<lpage>998</lpage>
<pmc-comment>elocation-id from pubmed: 10.1158/2159-8290.CD-17-0419</pmc-comment>
<abstract><p id="P1">High-grade epithelial ovarian carcinomas containing mutated <italic>BRCA1</italic>
or <italic>BRCA2</italic>
(<italic>BRCA1/2</italic>
) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and PARP inhibitors (PARPi), while restoration of HR function due to secondary mutations in <italic>BRCA1/2</italic>
has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pretreatment and postprogression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase II study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed ovarian carcinoma. In 6 of 12 pretreatment biopsies, a truncation mutation in <italic>BRCA1, RAD51C,</italic>
or <italic>RAD51D</italic>
was identified. In five of six paired postprogression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for <italic>RAD51C</italic>
. <italic>In vitro</italic>
complementation assays and a patient-derived xenograft, as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations.</p>
<sec id="S1"><title>Significance</title>
<p id="P2">Analyses of primary and secondary mutations in <italic>RAD51C</italic>
and <italic>RAD51D</italic>
provide evidence for these primary mutations in conferring PARPi sensitivity and secondary mutations as a mechanism of acquired PARPi resistance. PARPi resistance due to secondary mutations underpins the need for early delivery of PARPi therapy and for combination strategies.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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