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

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 o...

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Bibliographic Details
Authors: Osorio, Ana|||0000-0001-8124-3984, Bogliolo, Massimo|||0000-0001-8240-7784, Fernández, Victoria, Barroso, Alicia, De la Hoya, Miguel|||0000-0002-8113-1410, Caldes, Trinidad, Lasa, Adriana|||0000-0001-9957-9646, Ramon y Cajal, Teresa|||0000-0003-3490-3585, Santamariña, Marta, Vega, Ana|||0000-0002-7416-5137, Quiles, Francisco, Lázaro García, Conxi|||0000-0002-7198-5906, Diez, Orland|||0000-0001-7339-0570, Fernández García, Daniel, González-Sarmiento, Rogelio|||0000-0002-2726-6795, Durán, Mercedes|||0000-0002-6301-9732, Fernández Piqueras, José, Marín, Maria, Pujol Calvet, Maria Roser|||0000-0003-1840-5455, Surralles, Jordi|||0000-0002-4041-7519, Benitez, Javier|||0000-0002-0923-7202
Format: article
Publication Date:2013
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:132519
Online Access:https://ddd.uab.cat/record/132519
https://dx.doi.org/urn:doi:10.1002/humu.22438
Access Level:Open access
Keyword:Fanconi anemia
Breast cancer
ERCC4
FANCQ
XPF
Description
Summary: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.

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