title: Evaluation of rare variants in the new fanconi anemia gene ERCC4 (FANCQ) as familial breast/ovarian cancer susceptibility alleles.
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.
authors.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.forename: Massimo
authors.initials: M
authors.lastname: Bogliolo
authors.forename: Victoria
authors.initials: V
authors.lastname: Fernández
authors.forename: Alicia
authors.initials: A
authors.lastname: Barroso
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Adriana
authors.initials: A
authors.lastname: Lasa
authors.forename: Teresa
authors.initials: T
authors.lastname: Ramón y Cajal
authors.forename: Marta
authors.initials: M
authors.lastname: Santamariña
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Francisco
authors.initials: F
authors.lastname: Quiles
authors.forename: Conxi
authors.initials: C
authors.lastname: Lázaro
authors.forename: Orland
authors.initials: O
authors.lastname: Díez
authors.forename: Daniel
authors.initials: D
authors.lastname: Fernández
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.forename: Mercedes
authors.initials: M
authors.lastname: Durán
authors.forename: José Fernández
authors.initials: JF
authors.lastname: Piqueras
authors.forename: Maria
authors.initials: M
authors.lastname: Marín
authors.forename: Roser
authors.initials: R
authors.lastname: Pujol
authors.forename: Jordi
authors.initials: J
authors.lastname: Surrallés
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D061325:Hereditary Breast and Ovarian Cancer Syndrome; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D013030:Spain
chemical_list: D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein
keywords: ERCC4; FANCQ; Fanconi anemia; XPF; breast cancer