| Affiliation: | 1. Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, , CNIO, Madrid, Spain;2. Centre for Biomedical Network Research on Rare Diseases (CIBERER), , Spain;3. Genome Instability and DNA Repair Group, Department of Genetics and Microbiology, Universitat Autonoma de Barcelona (UAB), , Barcelona, Spain;4. Molecular Oncology Laboratory, Hospital Clínico San Carlos. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), , Barcelona, Spain;5. Genetics Service, Hospital de la Santa Creu i Sant Pau, , Barcelona, Spain;6. Oncology Service, Hospital de la Santa Creu i Sant Pau, , Barcelona, Spain;7. Grupo de Medicina Xenómica ‐USC, University of Santiago de Compostela, CIBERER,IDIS, , Santiago de Compostela, Spain;8. Fundación Pública Galega de Medicina Xenómica‐SERGAS Santiago de Compostela, , Spain;9. Hereditary Cancer Program, Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet, , Barcelona, Spain;10. Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, and University Hospital of Vall d'Hebron, , Barcelona, Spain;11. Instituto de Biología Molecular y Celular del Cancer (IBMCC), laboratory 14, Universidad de Salamanca‐CSIC, , Salamanca, Spain;12. Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM‐UVA), , Valladolid, Spain;13. Centro de Biología Molecular Severo Ochoa (CBM), Consejo Superior de Investigaciones Científicas‐Universidad Autónoma de Madrid, , Spain |
| 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. |
