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dc.contributor.authorFiglioli, G.
dc.contributor.authorBogliolo, M.
dc.contributor.authorCatucci, I.
dc.contributor.authorCaleca, L.
dc.contributor.authorLasheras, S. V.
dc.contributor.authorPujol, R.
dc.contributor.authorKiiski, J. I.
dc.contributor.authorMuranen, T. A.
dc.contributor.authorBarnes, D. R.
dc.contributor.authorDennis, J.
dc.contributor.authorMichailidou, K.
dc.contributor.authorBolla, M. K.
dc.contributor.authorLeslie, G.
dc.contributor.authorAalfs, C. M.
dc.contributor.authorBalleine, R.
dc.contributor.authorBaxter, R.
dc.contributor.authorBraye, S.
dc.contributor.authorCarpenter, J.
dc.contributor.authorDahlstrom, J.
dc.contributor.authorForbes, J.
dc.contributor.authorLee, C. S.
dc.contributor.authorMarsh, D.
dc.contributor.authorMorey, A.
dc.contributor.authorPathmanathan, N.
dc.contributor.authorScott, R.
dc.contributor.authorSimpson, P.
dc.contributor.authorSpigelman, A.
dc.contributor.authorWilcken, N.
dc.contributor.authorYip, D.
dc.contributor.authorZeps, N.
dc.contributor.authorAdank, M. A.
dc.contributor.authorAdlard, J.
dc.contributor.authorAgata, S.
dc.contributor.authorCadoo, K.
dc.contributor.authorAgnarsson, B. A.
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dc.contributor.authorAntonenkova, N. N.
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dc.contributor.authorSaunders, C.
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dc.contributor.authorSantamaría Cadavid, María 
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dc.contributor.authorWendt, C.
dc.contributor.authorWieme, G.
dc.contributor.authorWolk, A.
dc.contributor.authorYang, X. R.
dc.contributor.authorZheng, W.
dc.contributor.authorZiogas, A.
dc.contributor.authorZorn, K. K.
dc.contributor.authorDunning, A. M.
dc.contributor.authorLush, M.
dc.contributor.authorWang, Q.
dc.contributor.authorMcGuffog, L.
dc.contributor.authorParsons, M. T.
dc.contributor.authorPharoah, P. D. P.
dc.contributor.authorFostira, F.
dc.contributor.authorToland, A. E.
dc.contributor.authorAndrulis, I. L.
dc.contributor.authorRamus, S. J.
dc.contributor.authorSwerdlow, A. J.
dc.contributor.authorGreene, M. H.
dc.contributor.authorChung, W. K.
dc.contributor.authorMilne, R. L.
dc.contributor.authorChenevix-Trench, G.
dc.contributor.authorDörk, T.
dc.contributor.authorSchmidt, M. K.
dc.contributor.authorEaston, D. F.
dc.contributor.authorRadice, P.
dc.contributor.authorHahnen, E.
dc.contributor.authorAntoniou, A. C.
dc.contributor.authorCouch, F. J.
dc.contributor.authorNevanlinna, H.
dc.contributor.authorSurrallés, J.
dc.contributor.authorPeterlongo, P.
dc.date.accessioned2021-12-02T10:39:13Z
dc.date.available2021-12-02T10:39:13Z
dc.date.issued2019
dc.identifier.issn2374-4677
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825205/pdf/41523_2019_Article_127.pdfes
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pubmed/31700994es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/15789
dc.description.abstractBreast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM (-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.en
dc.language.isoenges
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleThe FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast canceren
dc.typeArtigoes
dc.authorsophosFiglioli, G.
dc.authorsophosBogliolo, M.
dc.authorsophosCatucci, I.
dc.authorsophosCaleca, L.
dc.authorsophosLasheras, S. V.
dc.authorsophosPujol, R.
dc.authorsophosKiiski, J. I.
dc.authorsophosMuranen, T. A.
dc.authorsophosBarnes, D. R.
dc.authorsophosDennis, J.
dc.authorsophosMichailidou, K.
dc.authorsophosBolla, M. K.
dc.authorsophosLeslie, G.
dc.authorsophosAalfs, C. M.
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dc.authorsophosBaxter, R.
dc.authorsophosBraye, S.
dc.authorsophosCarpenter, J.
dc.authorsophosDahlstrom, J.
dc.authorsophosForbes, J.
dc.authorsophosLee, C. S.
dc.authorsophosMarsh, D.
dc.authorsophosMorey, A.
dc.authorsophosPathmanathan, N.
dc.authorsophosScott, R.
dc.authorsophosSimpson, P.
dc.authorsophosSpigelman, A.
dc.authorsophosWilcken, N.
dc.authorsophosYip, D.
dc.authorsophosZeps, N.
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dc.authorsophosAmbrosone, C. B.
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dc.authorsophosAnton-Culver, H.
dc.authorsophosAntonenkova, N. N.
dc.authorsophosArndt, V.
dc.authorsophosArnold, N.
dc.authorsophosAronson, K. J.
dc.authorsophosArun, B. K.
dc.authorsophosAsseryanis, E.
dc.authorsophosAuber, B.
dc.authorsophosAuvinen, P.
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dc.authorsophosZheng, W.
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dc.authorsophosLush, M.
dc.authorsophosWang, Q.
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dc.authorsophosParsons, M. T.
dc.authorsophosPharoah, P. D. P.
dc.authorsophosFostira, F.
dc.authorsophosToland, A. E.
dc.authorsophosAndrulis, I. L.
dc.authorsophosRamus, S. J.
dc.authorsophosSwerdlow, A. J.
dc.authorsophosGreene, M. H.
dc.authorsophosChung, W. K.
dc.authorsophosMilne, R. L.
dc.authorsophosChenevix-Trench, G.
dc.authorsophosDörk, T.
dc.authorsophosSchmidt, M. K.
dc.authorsophosEaston, D. F.
dc.authorsophosRadice, P.
dc.authorsophosHahnen, E.
dc.authorsophosAntoniou, A. C.
dc.authorsophosCouch, F. J.
dc.authorsophosNevanlinna, H.
dc.authorsophosSurrallés, J.
dc.authorsophosPeterlongo, P.
dc.authorsophosInvestigators, Abctb
dc.authorsophosCollaborators, Gemo Study
dc.authorsophosKconFab
dc.identifier.doi10.1038/s41523-019-0127-5
dc.identifier.pmid31700994
dc.identifier.sophos31738
dc.issue.number1es
dc.journal.titleNPJ BREAST CANCERes
dc.organizationServizo Galego de Saúde::Dirección Xeral de Asistencia Sanitaria::Fundación Pública Galega de Medicina Xenómicaes
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Biomédica Ourense-Pontevedra-Vigo (IBI)es
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS)es
dc.rights.accessRightsopenAccesses
dc.subject.keywordFPGMXes
dc.subject.keywordIISGSes
dc.subject.keywordIDISes
dc.typefidesArtículo Originales
dc.typesophosArtículo Originales
dc.volume.number5es


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