Show simple item record

dc.contributor.authorRivera, B
dc.contributor.authorDi Iorio, M
dc.contributor.authorFrankum, J
dc.contributor.authorNadaf, J
dc.contributor.authorFahiminiya, S
dc.contributor.authorArcand, SL
dc.contributor.authorBurk, DL
dc.contributor.authorGrapton, D
dc.contributor.authorTomiak, E
dc.contributor.authorHastings, V
dc.contributor.authorHamel, N
dc.contributor.authorWagener, R
dc.contributor.authorAleynikova, O
dc.contributor.authorGiroux, S
dc.contributor.authorHamdan, FF
dc.contributor.authorDionne-Laporte, A
dc.contributor.authorZogopoulos, G
dc.contributor.authorRousseau, F
dc.contributor.authorBerghuis, AM
dc.contributor.authorProvencher, D
dc.contributor.authorRouleau, GA
dc.contributor.authorMichaud, JL
dc.contributor.authorMes-Masson, A-M
dc.contributor.authorMajewski, J
dc.contributor.authorBens, S
dc.contributor.authorSiebert, R
dc.contributor.authorNarod, SA
dc.contributor.authorAkbari, MR
dc.contributor.authorLord, CJ
dc.contributor.authorTonin, PN
dc.contributor.authorOrthwein, A
dc.contributor.authorFoulkes, WD
dc.date.accessioned2020-09-30T09:20:53Z
dc.date.issued2017-08
dc.identifier.citationCancer research, 2017, 77 (16), pp. 4517 - 4529
dc.identifier.issn0008-5472
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4080
dc.identifier.eissn1538-7445
dc.identifier.doi10.1158/0008-5472.can-17-0190
dc.description.abstractRAD51D is a key player in DNA repair by homologous recombination (HR), and RAD51D truncating variant carriers have an increased risk for ovarian cancer. However, the contribution of nontruncating RAD51D variants to cancer predisposition remains uncertain. Using deep sequencing and case-control genotyping studies, we show that in French Canadians, the missense RAD51D variant c.620C>T;p.S207L is highly prevalent and is associated with a significantly increased risk for ovarian high-grade serous carcinoma (HGSC; 3.8% cases vs. 0.2% controls). The frequency of the p.S207L variant did not significantly differ from that of controls in breast, endometrial, pancreas, or colorectal adenocarcinomas. Functionally, we show that this mutation impairs HR by disrupting the RAD51D-XRCC2 interaction and confers PARP inhibitor sensitivity. These results highlight the importance of a functional RAD51D-XRCC2 interaction to promote HR and prevent the development of HGSC. This study identifies c.620C>T;p.S207L as the first bona fide pathogenic RAD51D missense cancer susceptibility allele and supports the use of targeted PARP-inhibitor therapies in ovarian cancer patients carrying deleterious missense RAD51D variants. Cancer Res; 77(16); 4517-29. ©2017 AACR .
dc.formatPrint-Electronic
dc.format.extent4517 - 4529
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectOvarian Neoplasms
dc.subjectDNA-Binding Proteins
dc.subjectCase-Control Studies
dc.subjectPedigree
dc.subjectGenotype
dc.subjectMutation
dc.subjectMutation, Missense
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.titleFunctionally Null <i>RAD51D</i> Missense Mutation Associates Strongly with Ovarian Carcinoma.
dc.typeJournal Article
dcterms.dateAccepted2017-06-06
rioxxterms.versionofrecord10.1158/0008-5472.can-17-0190
rioxxterms.licenseref.startdate2017-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer research
pubs.issue16
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.publication-statusPublished
pubs.volume77
pubs.embargo.termsNot known
icr.researchteamGene Functionen_US
dc.contributor.icrauthorLord, Christopheren


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record