Evaluation of Rare Variants in the New Fanconi Anemia Gene ERCC4 (FANCQ) as Familial Breast/Ovarian Cancer Susceptibility Alleles
Por:
Osorio, A, Bogliolo, M, Fernandez, V, Barroso, A, de la Hoya, M, Caldes, T, Lasa, A, Cajal, TRY, Santamarina, M, Vega, A, Quiles, F, Lazaro, C, Diez, O, Fernandez, D, Gonzalez-Sarmiento, R, Duran, M, Piqueras, JF, Marin, M, Pujol, R, Surralles, J, Benitez, J
Publicada:
1 dic 2013
Resumen:
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 FAERCC4 mutations specifically disrupting interstrand cross-link repair. (C) 2013 Wiley Periodicals, Inc.
Filiaciones:
Osorio, A:
CNIO, Human Genet Grp, Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain
Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Bogliolo, M:
Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
UAB, Dept Genet & Microbiol, Genome Instabil & DNA Repair Grp, Barcelona, Spain
Fernandez, V:
CNIO, Human Genet Grp, Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain
Barroso, A:
CNIO, Human Genet Grp, Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain
de la Hoya, M:
Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Mol Oncol Lab, Hosp Clin San Carlos, Barcelona, Spain
Caldes, T:
Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Mol Oncol Lab, Hosp Clin San Carlos, Barcelona, Spain
Lasa, A:
Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain
Cajal, TRY:
Hosp Santa Creu & Sant Pau, Oncol Serv, Barcelona, Spain
Santamarina, M:
Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Univ Santiago de Compostela, CIBERER, IDIS, Grp Med Xenom USC, Santiago De Compostela, Spain
Vega, A:
Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Fdn Publ Galega Med Xenom SERGAS Santiago de Comp, Madrid, Spain
Quiles, F:
Hosp Duran & Reynals, Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Program, ICO, Barcelona, Spain
Lazaro, C:
Hosp Duran & Reynals, Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Program, ICO, Barcelona, Spain
Diez, O:
Univ Autonoma Barcelona, Oncogenet Lab, VHIO, VHIR, E-08193 Barcelona, Spain
Univ Hosp Vall dHebron, Barcelona, Spain
Fernandez, D:
Univ Salamanca, CSIC, IBMCC, Lab 14, E-37008 Salamanca, Spain
Gonzalez-Sarmiento, R:
Univ Salamanca, CSIC, IBMCC, Lab 14, E-37008 Salamanca, Spain
Duran, M:
Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain
Piqueras, JF:
Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa CBM, CSIC, E-28049 Madrid, Spain
Marin, M:
UAB, Dept Genet & Microbiol, Genome Instabil & DNA Repair Grp, Barcelona, Spain
Pujol, R:
Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
UAB, Dept Genet & Microbiol, Genome Instabil & DNA Repair Grp, Barcelona, Spain
Surralles, J:
Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
UAB, Dept Genet & Microbiol, Genome Instabil & DNA Repair Grp, Barcelona, Spain
Benitez, J:
CNIO, Human Genet Grp, Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain
Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Open Access
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