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

Hum Mutat. 2013 Dec;34(12):1615-8. doi: 10.1002/humu.22438.

Ana Osorio ¹, Massimo Bogliolo, Victoria Fernández, Alicia Barroso, Miguel de la Hoya, Trinidad Caldés, Adriana Lasa, Teresa Ramón y Cajal, Marta Santamariña, Ana Vega, Francisco Quiles, Conxi Lázaro, Orland Díez, Daniel Fernández, Rogelio González-Sarmiento, Mercedes Durán, José Fernández Piqueras, Maria Marín, Roser Pujol, Jordi Surrallés, Javier Benítez

Affiliations

Affiliation

1 Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, CNIO, Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain.

PMID: 24027083 DOI: 10.1002/humu.22438

Abstract

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.

Keywords

ERCC4; FANCQ; Fanconi anemia; XPF; breast cancer.

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