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Increased incidence of pathogenic variants in ATM in the context of testing for breast and ovarian cancer predisposition

dc.rights.licenseopenen_US
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorMACQUERE, Pierre
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorORAZIO, Sebastien
hal.structure.identifierBordeaux population health [BPH]
hal.structure.identifierGlobal Health in the Global South [GHiGS]
dc.contributor.authorBONNET, Fabrice
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorJONES, N.
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorBUBIEN, Virginie
dc.contributor.authorCHIRON, J.
dc.contributor.authorLAFON, D.
dc.contributor.authorBAROUK-SIMONET, E.
dc.contributor.authorTINAT, J.
dc.contributor.authorVENAT-BOUVET, L.
dc.contributor.authorGESTA, P.
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorLONGY, Michel
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorSEVENET, N.
dc.date.accessioned2022-03-07T09:47:23Z
dc.date.available2022-03-07T09:47:23Z
dc.date.issued2022-01-12
dc.identifier.issn1435-232X (Electronic) 1434-5161 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/128839
dc.description.abstractEnPathogenic Variants (PV) in major cancer predisposition genes are only identified in approximately 10% of patients with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Next Generation Sequencing (NGS) leads to the characterization of incidental variants in genes other than those known to be associated with HBOC syndrome. The aim of this study was to determine if such incidental PV were specific to a phenotype. The detection rates of HBOC-associated and incidental PV in 1812 patients who underwent genetic testing were compared with rates in control groups FLOSSIES and ExAC. The rates of incidental PV in the PALB2, ATM and CHEK2 genes were significantly increased in the HBOC group compared to controls with, respective odds ratios of 15.2 (95% CI = 5.6-47.6), 9.6 (95% CI = 4.8-19.6) and 2.7 (95% CI = 1.3-5.5). Unsupervised Hierarchical Clustering on Principle Components characterized 3 clusters: by HBOC (P = 0.01); by ExAC and FLOSSIES (P = 0.01 and 0.02 respectively); and by HBOC, ExAC and FLOSSIES (P = 0.01, 0.04 and 0.04 respectively). Interestingly, PALB2 and ATM were grouped in the same statistical cluster defined by the HBOC group, whereas CHEK2 was in a different cluster. We identified co-occurrences of PV in ATM and BRCA genes and confirmed the Manchester Scoring System as a reliable PV predictor tool for BRCA genes but not for ATM or PALB2. This study demonstrates that ATM PV, and to a lesser extent CHEK2 PV, are associated with HBOC syndrome. The co-occurrence of ATM PV with BRCA PV suggests that such ATM variants are not sufficient alone to induce cancer, supporting a multigenism hypothesis.
dc.language.isoENen_US
dc.title.enIncreased incidence of pathogenic variants in ATM in the context of testing for breast and ovarian cancer predisposition
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s10038-022-01014-3en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed35017683en_US
bordeaux.journalJournal of Human Geneticsen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamEPICENE_BPHen_US
bordeaux.teamGHIGS_BPHen_US
bordeaux.teamMORPH3Eusen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03599468
hal.version1
hal.date.transferred2022-03-07T09:47:26Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Human%20Genetics&rft.date=2022-01-12&rft.eissn=1435-232X%20(Electronic)%201434-5161%20(Linking)&rft.issn=1435-232X%20(Electronic)%201434-5161%20(Linking)&rft.au=MACQUERE,%20Pierre&ORAZIO,%20Sebastien&BONNET,%20Fabrice&JONES,%20N.&BUBIEN,%20Virginie&rft.genre=article


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