Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Identifieur interne : 004929 ( Ncbi/Merge ); précédent : 004928; suivant : 004930Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Auteurs : Olga Kondrashova [Australie] ; Minh Nguyen [États-Unis] ; Kristy Shield-Artin [Australie] ; Anna V. Tinker [Canada] ; Nelson N. H. Teng [États-Unis] ; Maria I. Harrell [États-Unis] ; Michael J. Kuiper [Australie] ; Gwo-Yaw Ho [Australie] ; Holly Barker [Australie] ; Maria Jasin [États-Unis] ; Rohit Prakash [États-Unis] ; Elizabeth M. Kass [États-Unis] ; Meghan R. Sullivan [États-Unis] ; Gregory J. Brunette [États-Unis] ; Kara A. Bernstein [États-Unis] ; Robert L. Coleman [États-Unis] ; Anne Floquet [France] ; Michael Friedlander [Australie] ; Ganessan Kichenadasse [Australie] ; David M. O'Malley [États-Unis] ; Amit Oza [Canada] ; James Sun [États-Unis] ; Liliane Robillard [États-Unis] ; Lara Maloney [États-Unis] ; Heidi Giordano [États-Unis] ; Matthew J. Wakefield [Australie] ; Scott H. Kaufmann [États-Unis] ; Andrew D. Simmons [États-Unis] ; Thomas C. Harding [États-Unis] ; Mitch Raponi [États-Unis] ; Iain A. Mcneish [Royaume-Uni] ; Elizabeth M. Swisher [États-Unis] ; Kevin K. Lin [États-Unis] ; Clare L. Scott [Australie]Source :
- Cancer discovery [ 2159-8274 ] ; 2017.
Abstract
High-grade epithelial ovarian carcinomas containing mutated
Analyses of primary and secondary mutations in
Url:
DOI: 10.1158/2159-8290.CD-17-0419
PubMed: 28588062
PubMed Central: 5612362
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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>
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<author><name sortKey="Bernstein, Kara A" sort="Bernstein, Kara A" uniqKey="Bernstein K" first="Kara A." last="Bernstein">Kara A. Bernstein</name>
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<author><name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L." last="Coleman">Robert L. Coleman</name>
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<author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
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<author><name sortKey="Swisher, Elizabeth M" sort="Swisher, Elizabeth M" uniqKey="Swisher E" first="Elizabeth M." last="Swisher">Elizabeth M. Swisher</name>
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<author><name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L." last="Scott">Clare L. Scott</name>
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<affiliation wicri:level="1"><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
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<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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nguyen, Minh" sort="Nguyen, Minh" uniqKey="Nguyen M" first="Minh" last="Nguyen">Minh Nguyen</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="1"><nlm:aff id="A4">British Columbia Cancer Agency, Vancouver, British Columbia, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>British Columbia Cancer Agency, Vancouver, British Columbia</wicri:regionArea>
<wicri:noRegion>British Columbia</wicri:noRegion>
</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 wicri:level="2"><nlm:aff id="A5">Stanford University, Palo Alto, California</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Stanford University, Palo Alto</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</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 wicri:level="4"><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jasin, Maria" sort="Jasin, Maria" uniqKey="Jasin M" first="Maria" last="Jasin">Maria Jasin</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Prakash, Rohit" sort="Prakash, Rohit" uniqKey="Prakash R" first="Rohit" last="Prakash">Rohit Prakash</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A11">The University of Texas MD Anderson Cancer Center, Houston, Texas</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>The University of Texas MD Anderson Cancer Center, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
<affiliation wicri:level="3"><nlm:aff id="A12">Institut Bergonié, Bordeaux, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Bergonié, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Friedlander, Michael" sort="Friedlander, Michael" uniqKey="Friedlander M" first="Michael" last="Friedlander">Michael Friedlander</name>
<affiliation wicri:level="1"><nlm:aff id="A13">University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales</wicri:regionArea>
<wicri:noRegion>New South Wales</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kichenadasse, Ganessan" sort="Kichenadasse, Ganessan" uniqKey="Kichenadasse G" first="Ganessan" last="Kichenadasse">Ganessan Kichenadasse</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Flinders University, Adelaide, South Australia, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Flinders University, Adelaide, South Australia</wicri:regionArea>
<wicri:noRegion>South Australia</wicri:noRegion>
</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 wicri:level="2"><nlm:aff id="A15">The Ohio State University, James Cancer Center, Columbus, Ohio</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>The Ohio State University, James Cancer Center, Columbus</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Oza, Amit" sort="Oza, Amit" uniqKey="Oza A" first="Amit" last="Oza">Amit Oza</name>
<affiliation wicri:level="1"><nlm:aff id="A16">Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<affiliation wicri:level="2"><nlm:aff id="A17">Foundation Medicine, Inc., Cambridge, Massachusetts</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Foundation Medicine, Inc., Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Robillard, Liliane" sort="Robillard, Liliane" uniqKey="Robillard L" first="Liliane" last="Robillard">Liliane Robillard</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="2"><nlm:aff id="A21">Mayo Clinic Cancer Center, Rochester, Minnesota</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Mayo Clinic Cancer Center, Rochester</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="4"><nlm:aff id="A22">Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Sciences, University of Glasgow, Glasgow</wicri:regionArea>
<orgName type="university">Université de Glasgow</orgName>
<placeName><settlement type="city">Glasgow</settlement>
<region type="country">Écosse</region>
</placeName>
</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 wicri:level="2"><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</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>
<double pmid="28588062"><pmc><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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Nguyen, Minh" sort="Nguyen, Minh" uniqKey="Nguyen M" first="Minh" last="Nguyen">Minh Nguyen</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
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<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
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<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="1"><nlm:aff id="A4">British Columbia Cancer Agency, Vancouver, British Columbia, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>British Columbia Cancer Agency, Vancouver, British Columbia</wicri:regionArea>
<wicri:noRegion>British Columbia</wicri:noRegion>
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<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 wicri:level="2"><nlm:aff id="A5">Stanford University, Palo Alto, California</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Stanford University, Palo Alto</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</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 wicri:level="4"><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
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<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
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<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jasin, Maria" sort="Jasin, Maria" uniqKey="Jasin M" first="Maria" last="Jasin">Maria Jasin</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Prakash, Rohit" sort="Prakash, Rohit" uniqKey="Prakash R" first="Rohit" last="Prakash">Rohit Prakash</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A11">The University of Texas MD Anderson Cancer Center, Houston, Texas</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>The University of Texas MD Anderson Cancer Center, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
<affiliation wicri:level="3"><nlm:aff id="A12">Institut Bergonié, Bordeaux, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Bergonié, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Friedlander, Michael" sort="Friedlander, Michael" uniqKey="Friedlander M" first="Michael" last="Friedlander">Michael Friedlander</name>
<affiliation wicri:level="1"><nlm:aff id="A13">University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Kichenadasse, Ganessan" sort="Kichenadasse, Ganessan" uniqKey="Kichenadasse G" first="Ganessan" last="Kichenadasse">Ganessan Kichenadasse</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Flinders University, Adelaide, South Australia, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Flinders University, Adelaide, South Australia</wicri:regionArea>
<wicri:noRegion>South Australia</wicri:noRegion>
</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 wicri:level="2"><nlm:aff id="A15">The Ohio State University, James Cancer Center, Columbus, Ohio</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>The Ohio State University, James Cancer Center, Columbus</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Oza, Amit" sort="Oza, Amit" uniqKey="Oza A" first="Amit" last="Oza">Amit Oza</name>
<affiliation wicri:level="1"><nlm:aff id="A16">Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<affiliation wicri:level="2"><nlm:aff id="A17">Foundation Medicine, Inc., Cambridge, Massachusetts</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Foundation Medicine, Inc., Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Robillard, Liliane" sort="Robillard, Liliane" uniqKey="Robillard L" first="Liliane" last="Robillard">Liliane Robillard</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="2"><nlm:aff id="A21">Mayo Clinic Cancer Center, Rochester, Minnesota</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Mayo Clinic Cancer Center, Rochester</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
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</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 wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
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</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 wicri:level="4"><nlm:aff id="A22">Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Sciences, University of Glasgow, Glasgow</wicri:regionArea>
<orgName type="university">Université de Glasgow</orgName>
<placeName><settlement type="city">Glasgow</settlement>
<region type="country">Écosse</region>
</placeName>
</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 wicri:level="2"><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lin, Kevin K" sort="Lin, Kevin K" uniqKey="Lin K" first="Kevin K." last="Lin">Kevin K. Lin</name>
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<country xml:lang="fr">États-Unis</country>
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</author>
<author><name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L." last="Scott">Clare L. Scott</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
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<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria</wicri:regionArea>
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<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>
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<country xml:lang="fr">Australie</country>
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<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Nguyen, Minh" sort="Nguyen, Minh" uniqKey="Nguyen M" first="Minh" last="Nguyen">Minh Nguyen</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Shield Artin, Kristy" sort="Shield Artin, Kristy" uniqKey="Shield Artin K" first="Kristy" last="Shield-Artin">Kristy Shield-Artin</name>
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<country xml:lang="fr">Australie</country>
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<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<author><name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V." last="Tinker">Anna V. Tinker</name>
<affiliation wicri:level="1"><nlm:aff id="A4">British Columbia Cancer Agency, Vancouver, British Columbia, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>British Columbia Cancer Agency, Vancouver, British Columbia</wicri:regionArea>
<wicri:noRegion>British Columbia</wicri:noRegion>
</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 wicri:level="2"><nlm:aff id="A5">Stanford University, Palo Alto, California</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Stanford University, Palo Alto</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</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 wicri:level="4"><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jasin, Maria" sort="Jasin, Maria" uniqKey="Jasin M" first="Maria" last="Jasin">Maria Jasin</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Prakash, Rohit" sort="Prakash, Rohit" uniqKey="Prakash R" first="Rohit" last="Prakash">Rohit Prakash</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A9">Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A10">Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A11">The University of Texas MD Anderson Cancer Center, Houston, Texas</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>The University of Texas MD Anderson Cancer Center, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
<affiliation wicri:level="3"><nlm:aff id="A12">Institut Bergonié, Bordeaux, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Bergonié, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Friedlander, Michael" sort="Friedlander, Michael" uniqKey="Friedlander M" first="Michael" last="Friedlander">Michael Friedlander</name>
<affiliation wicri:level="1"><nlm:aff id="A13">University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales</wicri:regionArea>
<wicri:noRegion>New South Wales</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kichenadasse, Ganessan" sort="Kichenadasse, Ganessan" uniqKey="Kichenadasse G" first="Ganessan" last="Kichenadasse">Ganessan Kichenadasse</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Flinders University, Adelaide, South Australia, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Flinders University, Adelaide, South Australia</wicri:regionArea>
<wicri:noRegion>South Australia</wicri:noRegion>
</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 wicri:level="2"><nlm:aff id="A15">The Ohio State University, James Cancer Center, Columbus, Ohio</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>The Ohio State University, James Cancer Center, Columbus</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Oza, Amit" sort="Oza, Amit" uniqKey="Oza A" first="Amit" last="Oza">Amit Oza</name>
<affiliation wicri:level="1"><nlm:aff id="A16">Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<affiliation wicri:level="2"><nlm:aff id="A17">Foundation Medicine, Inc., Cambridge, Massachusetts</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Foundation Medicine, Inc., Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Robillard, Liliane" sort="Robillard, Liliane" uniqKey="Robillard L" first="Liliane" last="Robillard">Liliane Robillard</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A7">Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="2"><nlm:aff id="A21">Mayo Clinic Cancer Center, Rochester, Minnesota</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Mayo Clinic Cancer Center, Rochester</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="4"><nlm:aff id="A22">Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Sciences, University of Glasgow, Glasgow</wicri:regionArea>
<orgName type="university">Université de Glasgow</orgName>
<placeName><settlement type="city">Glasgow</settlement>
<region type="country">Écosse</region>
</placeName>
</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 wicri:level="2"><nlm:aff id="A6">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</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 wicri:level="2"><nlm:aff id="A3">Clovis Oncology, Inc., Boulder, Colorado</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:aff id="A1">Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A2">Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Biology, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</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>
<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Secondary Somatic Mutations Restoring RAD51C and RAD51D 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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nguyen, Minh" sort="Nguyen, Minh" uniqKey="Nguyen M" first="Minh" last="Nguyen">Minh Nguyen</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</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 wicri:level="1"><nlm:affiliation>British Columbia Cancer Agency, Vancouver, British Columbia, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>British Columbia Cancer Agency, Vancouver, British Columbia</wicri:regionArea>
<wicri:noRegion>British Columbia</wicri:noRegion>
</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 wicri:level="2"><nlm:affiliation>Stanford University, Palo Alto, California.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Stanford University, Palo Alto</wicri:cityArea>
</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 wicri:level="2"><nlm:affiliation>University of Washington, Seattle, Washington.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</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 wicri:level="4"><nlm:affiliation>Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
<affiliation wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.</nlm:affiliation>
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</affiliation>
</author>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
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</affiliation>
</author>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</affiliation>
</author>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
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</affiliation>
</author>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
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</author>
<author><name sortKey="Bernstein, Kara A" sort="Bernstein, Kara A" uniqKey="Bernstein K" first="Kara A" last="Bernstein">Kara A. Bernstein</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
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</affiliation>
</author>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>The University of Texas MD Anderson Cancer Center, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
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<wicri:regionArea>Institut Bergonié, Bordeaux</wicri:regionArea>
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</placeName>
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</author>
<author><name sortKey="Friedlander, Michael" sort="Friedlander, Michael" uniqKey="Friedlander M" first="Michael" last="Friedlander">Michael Friedlander</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales</wicri:regionArea>
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</author>
<author><name sortKey="Kichenadasse, Ganessan" sort="Kichenadasse, Ganessan" uniqKey="Kichenadasse G" first="Ganessan" last="Kichenadasse">Ganessan Kichenadasse</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Flinders University, Adelaide, South Australia</wicri:regionArea>
<wicri:noRegion>South Australia</wicri:noRegion>
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</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 wicri:level="2"><nlm:affiliation>The Ohio State University, James Cancer Center, Columbus, Ohio.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>The Ohio State University, James Cancer Center, Columbus</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Oza, Amit" sort="Oza, Amit" uniqKey="Oza A" first="Amit" last="Oza">Amit Oza</name>
<affiliation wicri:level="1"><nlm:affiliation>Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
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</author>
<author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<affiliation wicri:level="2"><nlm:affiliation>Foundation Medicine, Inc., Cambridge, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Foundation Medicine, Inc., Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Robillard, Liliane" sort="Robillard, Liliane" uniqKey="Robillard L" first="Liliane" last="Robillard">Liliane Robillard</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Bowtell, David" sort="Bowtell, David" uniqKey="Bowtell D" first="David" last="Bowtell">David Bowtell</name>
</author>
<author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
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</author>
<author><name sortKey="Kaufmann, Scott H" sort="Kaufmann, Scott H" uniqKey="Kaufmann S" first="Scott H" last="Kaufmann">Scott H. Kaufmann</name>
<affiliation wicri:level="2"><nlm:affiliation>Mayo Clinic Cancer Center, Rochester, Minnesota.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Mayo Clinic Cancer Center, Rochester</wicri:cityArea>
</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 wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
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</author>
<author><name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A" last="Mcneish">Iain A. Mcneish</name>
<affiliation wicri:level="4"><nlm:affiliation>Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<region type="country">Écosse</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>University of Washington, Seattle, Washington.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
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</author>
<author><name sortKey="Lin, Kevin K" sort="Lin, Kevin K" uniqKey="Lin K" first="Kevin K" last="Lin">Kevin K. Lin</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. scottc@wehi.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Secondary Somatic Mutations Restoring RAD51C and RAD51D 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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nguyen, Minh" sort="Nguyen, Minh" uniqKey="Nguyen M" first="Minh" last="Nguyen">Minh Nguyen</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
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</author>
<author><name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V" last="Tinker">Anna V. Tinker</name>
<affiliation wicri:level="1"><nlm:affiliation>British Columbia Cancer Agency, Vancouver, British Columbia, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>British Columbia Cancer Agency, Vancouver, British Columbia</wicri:regionArea>
<wicri:noRegion>British Columbia</wicri:noRegion>
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</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 wicri:level="2"><nlm:affiliation>Stanford University, Palo Alto, California.</nlm:affiliation>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
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<wicri:cityArea>Stanford University, Palo Alto</wicri:cityArea>
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<author><name sortKey="Harrell, Maria I" sort="Harrell, Maria I" uniqKey="Harrell M" first="Maria I" last="Harrell">Maria I. Harrell</name>
<affiliation wicri:level="2"><nlm:affiliation>University of Washington, Seattle, Washington.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
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</author>
<author><name sortKey="Kuiper, Michael J" sort="Kuiper, Michael J" uniqKey="Kuiper M" first="Michael J" last="Kuiper">Michael J. Kuiper</name>
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<country xml:lang="fr">Australie</country>
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</author>
<author><name sortKey="Ho, Gwo Yaw" sort="Ho, Gwo Yaw" uniqKey="Ho G" first="Gwo-Yaw" last="Ho">Gwo-Yaw Ho</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
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<author><name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
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<author><name sortKey="Jasin, Maria" sort="Jasin, Maria" uniqKey="Jasin M" first="Maria" last="Jasin">Maria Jasin</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
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<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
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</author>
<author><name sortKey="Prakash, Rohit" sort="Prakash, Rohit" uniqKey="Prakash R" first="Rohit" last="Prakash">Rohit Prakash</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
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</author>
<author><name sortKey="Kass, Elizabeth M" sort="Kass, Elizabeth M" uniqKey="Kass E" first="Elizabeth M" last="Kass">Elizabeth M. Kass</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
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</author>
<author><name sortKey="Sullivan, Meghan R" sort="Sullivan, Meghan R" uniqKey="Sullivan M" first="Meghan R" last="Sullivan">Meghan R. Sullivan</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
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<author><name sortKey="Brunette, Gregory J" sort="Brunette, Gregory J" uniqKey="Brunette G" first="Gregory J" last="Brunette">Gregory J. Brunette</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
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</author>
<author><name sortKey="Bernstein, Kara A" sort="Bernstein, Kara A" uniqKey="Bernstein K" first="Kara A" last="Bernstein">Kara A. Bernstein</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
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</author>
<author><name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L" last="Coleman">Robert L. Coleman</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
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<wicri:cityArea>The University of Texas MD Anderson Cancer Center, Houston</wicri:cityArea>
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</author>
<author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
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<country xml:lang="fr">France</country>
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<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
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</placeName>
</affiliation>
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<author><name sortKey="Friedlander, Michael" sort="Friedlander, Michael" uniqKey="Friedlander M" first="Michael" last="Friedlander">Michael Friedlander</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>University of New South Wales and Prince of Wales Hospital, Sydney, New South Wales</wicri:regionArea>
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</author>
<author><name sortKey="Kichenadasse, Ganessan" sort="Kichenadasse, Ganessan" uniqKey="Kichenadasse G" first="Ganessan" last="Kichenadasse">Ganessan Kichenadasse</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Flinders University, Adelaide, South Australia</wicri:regionArea>
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</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 wicri:level="2"><nlm:affiliation>The Ohio State University, James Cancer Center, Columbus, Ohio.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>The Ohio State University, James Cancer Center, Columbus</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Oza, Amit" sort="Oza, Amit" uniqKey="Oza A" first="Amit" last="Oza">Amit Oza</name>
<affiliation wicri:level="1"><nlm:affiliation>Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<affiliation wicri:level="2"><nlm:affiliation>Foundation Medicine, Inc., Cambridge, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Foundation Medicine, Inc., Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Robillard, Liliane" sort="Robillard, Liliane" uniqKey="Robillard L" first="Liliane" last="Robillard">Liliane Robillard</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Bowtell, David" sort="Bowtell, David" uniqKey="Bowtell D" first="David" last="Bowtell">David Bowtell</name>
</author>
<author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</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 wicri:level="2"><nlm:affiliation>Mayo Clinic Cancer Center, Rochester, Minnesota.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Mayo Clinic Cancer Center, Rochester</wicri:cityArea>
</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 wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<affiliation wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="4"><nlm:affiliation>Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Sciences, University of Glasgow, Glasgow</wicri:regionArea>
<orgName type="university">Université de Glasgow</orgName>
<placeName><settlement type="city">Glasgow</settlement>
<region type="country">Écosse</region>
</placeName>
</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 wicri:level="2"><nlm:affiliation>University of Washington, Seattle, Washington.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</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 wicri:level="2"><nlm:affiliation>Clovis Oncology, Inc., Boulder, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Clovis Oncology, Inc., Boulder</wicri:cityArea>
</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 wicri:level="1"><nlm:affiliation>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. scottc@wehi.edu.au.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Cancer discovery</title>
<idno type="eISSN">2159-8290</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en">High-grade epithelial ovarian carcinomas containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and PARP inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 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 BRCA1, RAD51C, or RAD51D 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 RAD51CIn vitro complementation assays and a patient-derived xenograft, as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations.Significance: Analyses of primary and secondary mutations in RAD51C and RAD51D 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. Cancer Discov; 7(9); 984-98. ©2017 AACR.See related commentary by Domchek, p. 937See related article by Quigley et al., p. 999See related article by Goodall et al., p. 1006This article is highlighted in the In This Issue feature, p. 920.</div>
</front>
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