4 research outputs found

    Evaluation of rare variants in the new fanconi anemia gene ERCC4 (FANCQ) as familial breast/ovarian cancer susceptibility alleles

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    Recently, it has been reported that biallelic mutations in the ERCC4 (FANCQ) gene cause Fanconi anemia (FA) subtype FA-Q. To investigate the possible role of ERCC4 in breast and ovarian cancer susceptibility, as occurs with other FA genes, we screened the 11 coding exons and exon-intron boundaries of ERCC4 in 1573 index cases from high-risk Spanish familial breast and ovarian cancer pedigrees that had been tested negative for BRCA1 and BRCA2 mutations and 854 controls. The frequency of ERCC4 mutation carriers does not differ between cases and controls, suggesting that ERCC4 is not a cancer susceptibility gene. Interestingly, the prevalence of ERCC4 mutation carriers (one in 288) is similar to that reported for FANCA, whereas there are approximately 100-fold more FA-A than FA-Q patients, indicating that most biallelic combinations of ERCC4 mutations are embryo lethal. Finally, we identified additional bone-fide FA ERCC4 mutations specifically disrupting interstrand cross-link repai

    Evaluation of Rare Variants in the New Fanconi Anemia Gene ERCC4 (FANCQ) as Familial Breast/Ovarian Cancer Susceptibility Alleles

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    Recently, it has been reported that biallelic mutations in the ERCC4 (FANCQ) gene cause Fanconi anemia (FA) subtype FA-Q. To investigate the possible role of ERCC4 in breast and ovarian cancer susceptibility, as occurs with other FA genes, we screened the 11 coding exons and exon-intron boundaries of ERCC4 in 1573 index cases from high-risk Spanish familial breast and ovarian cancer pedigrees that had been tested negative for BRCA1 and BRCA2 mutations and 854 controls. The frequency of ERCC4 mutation carriers does not differ between cases and controls, suggesting that ERCC4 is not a cancer susceptibility gene. Interestingly, the prevalence of ERCC4 mutation carriers (one in 288) is similar to that reported for FANCA, whereas there are approximately 100-fold more FA-A than FA-Q patients, indicating that most biallelic combinations of ERCC4 mutations are embryo lethal. Finally, we identified additional bone-fide FA ERCC4 mutations specifically disrupting interstrand cross-link repair. © 2013 WILEY PERIODICALS, INC.Contract grant sponsors: Mutua Madrileña Foundation (FMMA); Intrasalud PI12/00070; Accion Cooperativa y Colaborativa Intramural-CIBER2012; SAF2010-20493; Generalitat de Catalunya (SGR0489-2009), the ICREA-Academia award, the Spanish Ministry of Economy and Competitiveness (CIBERER CB06/07/0023, SAF2009-11936 and SAF2012-31881); the European Regional Development FEDER Funds; Fondo de Investigacion Sanitaria (FIS) (PI 12/00539); European Regional Development FEDER Funds; Asociacion Española Contra el Cáncer; Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia (ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, and 2009SGR290). Accion Cooperativa y Colaborativa Intramural-CIBERER 2012, the OncoCycle Pro-gramme (S2011/BMD-2470) and SAF2012-36556); and Fondo de Investigacion Sanitaria (PI10/00219).Peer Reviewe
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