AustralieFrV1, Main, Exploration, bibRecord, 000392

Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Identifieur interne : 000392 ( Main/Exploration ); précédent : 000391; suivant : 000393

Secondary 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.

RBID : PMC:5612362

Abstract

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 RAD51C. In 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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612362

DOI: 10.1158/2159-8290.CD-17-0419
PubMed: 28588062
PubMed Central: 5612362

Affiliations:

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Secondary Somatic Mutations Restoring <italic>RAD51C</italic>
 and <italic>RAD51D</italic>
 Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma</title>
<author><name sortKey="Kondrashova, Olga" sort="Kondrashova, Olga" uniqKey="Kondrashova O" first="Olga" last="Kondrashova">Olga Kondrashova</name>
<affiliation 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>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">28588062</idno>
<idno type="pmc">5612362</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612362</idno>
<idno type="RBID">PMC:5612362</idno>
<idno type="doi">10.1158/2159-8290.CD-17-0419</idno>
<date when="2017">2017</date>
<idno type="wicri:Area/Pmc/Corpus">001E77</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E77</idno>
<idno type="wicri:Area/Pmc/Curation">001D33</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001D33</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000095</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000095</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">000647</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000647</idno>
<idno type="wicri:Area/PubMed/Curation">000645</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000645</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000645</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000645</idno>
<idno type="wicri:Area/Ncbi/Merge">004929</idno>
<idno type="wicri:Area/Ncbi/Curation">004929</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">004929</idno>
<idno type="wicri:doubleKey">2159-8274:2017:Kondrashova O:secondary:somatic:mutations</idno>
<idno type="wicri:Area/Main/Merge">000387</idno>
<idno type="wicri:Area/Main/Curation">000392</idno>
<idno type="wicri:Area/Main/Exploration">000392</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Secondary Somatic Mutations Restoring <italic>RAD51C</italic>
 and <italic>RAD51D</italic>
 Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma</title>
<author><name sortKey="Kondrashova, Olga" sort="Kondrashova, Olga" uniqKey="Kondrashova O" first="Olga" last="Kondrashova">Olga Kondrashova</name>
<affiliation 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>
<affiliations><list><country><li>Australie</li>
<li>Canada</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Aquitaine</li>
<li>Californie</li>
<li>Colorado</li>
<li>Massachusetts</li>
<li>Minnesota</li>
<li>Nouvelle-Aquitaine</li>
<li>Ohio</li>
<li>Pennsylvanie</li>
<li>Texas</li>
<li>Victoria (État)</li>
<li>Washington (État)</li>
<li>Écosse</li>
<li>État de New York</li>
</region>
<settlement><li>Bordeaux</li>
<li>Glasgow</li>
<li>Melbourne</li>
</settlement>
<orgName><li>Université de Glasgow</li>
<li>Université de Melbourne</li>
</orgName>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Kondrashova, Olga" sort="Kondrashova, Olga" uniqKey="Kondrashova O" first="Olga" last="Kondrashova">Olga Kondrashova</name>
</noRegion>
<name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
<name sortKey="Barker, Holly" sort="Barker, Holly" uniqKey="Barker H" first="Holly" last="Barker">Holly Barker</name>
<name sortKey="Friedlander, Michael" sort="Friedlander, Michael" uniqKey="Friedlander M" first="Michael" last="Friedlander">Michael Friedlander</name>
<name sortKey="Ho, Gwo Yaw" sort="Ho, Gwo Yaw" uniqKey="Ho G" first="Gwo-Yaw" last="Ho">Gwo-Yaw Ho</name>
<name sortKey="Ho, Gwo Yaw" sort="Ho, Gwo Yaw" uniqKey="Ho G" first="Gwo-Yaw" last="Ho">Gwo-Yaw Ho</name>
<name sortKey="Ho, Gwo Yaw" sort="Ho, Gwo Yaw" uniqKey="Ho G" first="Gwo-Yaw" last="Ho">Gwo-Yaw Ho</name>
<name sortKey="Kichenadasse, Ganessan" sort="Kichenadasse, Ganessan" uniqKey="Kichenadasse G" first="Ganessan" last="Kichenadasse">Ganessan Kichenadasse</name>
<name sortKey="Kondrashova, Olga" sort="Kondrashova, Olga" uniqKey="Kondrashova O" first="Olga" last="Kondrashova">Olga Kondrashova</name>
<name sortKey="Kuiper, Michael J" sort="Kuiper, Michael J" uniqKey="Kuiper M" first="Michael J." last="Kuiper">Michael J. Kuiper</name>
<name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L." last="Scott">Clare L. Scott</name>
<name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L." last="Scott">Clare L. Scott</name>
<name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L." last="Scott">Clare L. Scott</name>
<name sortKey="Shield Artin, Kristy" sort="Shield Artin, Kristy" uniqKey="Shield Artin K" first="Kristy" last="Shield-Artin">Kristy Shield-Artin</name>
<name sortKey="Shield Artin, Kristy" sort="Shield Artin, Kristy" uniqKey="Shield Artin K" first="Kristy" last="Shield-Artin">Kristy Shield-Artin</name>
<name sortKey="Wakefield, Matthew J" sort="Wakefield, Matthew J" uniqKey="Wakefield M" first="Matthew J." last="Wakefield">Matthew J. Wakefield</name>
<name sortKey="Wakefield, Matthew J" sort="Wakefield, Matthew J" uniqKey="Wakefield M" first="Matthew J." last="Wakefield">Matthew J. Wakefield</name>
</country>
<country name="États-Unis"><region name="Colorado"><name sortKey="Nguyen, Minh" sort="Nguyen, Minh" uniqKey="Nguyen M" first="Minh" last="Nguyen">Minh Nguyen</name>
</region>
<name sortKey="Bernstein, Kara A" sort="Bernstein, Kara A" uniqKey="Bernstein K" first="Kara A." last="Bernstein">Kara A. Bernstein</name>
<name sortKey="Brunette, Gregory J" sort="Brunette, Gregory J" uniqKey="Brunette G" first="Gregory J." last="Brunette">Gregory J. Brunette</name>
<name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L." last="Coleman">Robert L. Coleman</name>
<name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<name sortKey="Harding, Thomas C" sort="Harding, Thomas C" uniqKey="Harding T" first="Thomas C." last="Harding">Thomas C. Harding</name>
<name sortKey="Harrell, Maria I" sort="Harrell, Maria I" uniqKey="Harrell M" first="Maria I." last="Harrell">Maria I. Harrell</name>
<name sortKey="Jasin, Maria" sort="Jasin, Maria" uniqKey="Jasin M" first="Maria" last="Jasin">Maria Jasin</name>
<name sortKey="Kass, Elizabeth M" sort="Kass, Elizabeth M" uniqKey="Kass E" first="Elizabeth M." last="Kass">Elizabeth M. Kass</name>
<name sortKey="Kaufmann, Scott H" sort="Kaufmann, Scott H" uniqKey="Kaufmann S" first="Scott H." last="Kaufmann">Scott H. Kaufmann</name>
<name sortKey="Lin, Kevin K" sort="Lin, Kevin K" uniqKey="Lin K" first="Kevin K." last="Lin">Kevin K. Lin</name>
<name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
<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>
<name sortKey="Prakash, Rohit" sort="Prakash, Rohit" uniqKey="Prakash R" first="Rohit" last="Prakash">Rohit Prakash</name>
<name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<name sortKey="Robillard, Liliane" sort="Robillard, Liliane" uniqKey="Robillard L" first="Liliane" last="Robillard">Liliane Robillard</name>
<name sortKey="Simmons, Andrew D" sort="Simmons, Andrew D" uniqKey="Simmons A" first="Andrew D." last="Simmons">Andrew D. Simmons</name>
<name sortKey="Sullivan, Meghan R" sort="Sullivan, Meghan R" uniqKey="Sullivan M" first="Meghan R." last="Sullivan">Meghan R. Sullivan</name>
<name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<name sortKey="Swisher, Elizabeth M" sort="Swisher, Elizabeth M" uniqKey="Swisher E" first="Elizabeth M." last="Swisher">Elizabeth M. Swisher</name>
<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>
</country>
<country name="Canada"><noRegion><name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V." last="Tinker">Anna V. Tinker</name>
</noRegion>
<name sortKey="Oza, Amit" sort="Oza, Amit" uniqKey="Oza A" first="Amit" last="Oza">Amit Oza</name>
</country>
<country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
</region>
</country>
<country name="Royaume-Uni"><region name="Écosse"><name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A." last="Mcneish">Iain A. Mcneish</name>
</region>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000392 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000392 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:5612362
   |texte=   Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:28588062" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a AustralieFrV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Dec 5 10:43:12 2017. Site generation: Tue Mar 5 14:07:20 2024

Serveur d'exploration sur les relations entre la France et l'Australie

Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Source :

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.