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Evaluation of Rare Variants in the New F anconi Anemia Gene ERCC 4 ( FANCQ ) as Familial Breast/Ovarian Cancer Susceptibility Alleles
Author(s) -
Osorio Ana,
Bogliolo Massimo,
Fernández Victoria,
Barroso Alicia,
Hoya Miguel,
Caldés Trinidad,
Lasa Adriana,
Ramón y Cajal Teresa,
Santamariña Marta,
Vega Ana,
Quiles Francisco,
Lázaro Conxi,
Díez Orland,
Fernández Daniel,
GonzálezSarmiento Rogelio,
Durán Mercedes,
Piqueras José Fernández,
Marín Maria,
Pujol Roser,
Surrallés Jordi,
Benítez Javier
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22438
Subject(s) - biology , ovarian cancer , brca2 protein , genetics , fanconi anemia , fanca , allele , exon , breast cancer , brca mutation , gene , cancer research , mutation , cancer , germline mutation , dna repair
Recently, it has been reported that biallelic mutations in the ERCC 4 ( FANCQ ) gene cause F anconi anemia ( FA ) subtype FA ‐ Q . To investigate the possible role of ERCC 4 in breast and ovarian cancer susceptibility, as occurs with other FA genes, we screened the 11 coding exons and exon–intron boundaries of ERCC 4 in 1573 index cases from high‐risk S panish familial breast and ovarian cancer pedigrees that had been tested negative for BRCA 1 and BRCA 2 mutations and 854 controls. The frequency of ERCC 4 mutation carriers does not differ between cases and controls, suggesting that ERCC 4 is not a cancer susceptibility gene. Interestingly, the prevalence of ERCC 4 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 ERCC 4 mutations are embryo lethal. Finally, we identified additional bone‐fide FA ERCC 4 mutations specifically disrupting interstrand cross‐link repair.