title: Lack of germ-line mutations at the specific BRCA1-IRIS coding sequence in 114 Spanish high-risk breast/ovarian families.
abstract: A new BRCA1 locus product called BRCA1-IRIS has been identified recently. High-risk breast/ovarian families have not been screened for germ-line mutations at the specific BRCA1-IRIS coding sequence, as it was considered merely as part of BRCA1 intron 11. Here we report the first comprehensive screening of germ-line mutations in a cohort of 116 index cases from high-risk breast/ovarian families in which no germ-line mutation was identified in BRCA1 or BRCA2. We did not find germ-line mutations at the specific BRCA1-IRIS coding sequence in any sample. The only heterozygous patter identified by DGGE was caused by a C to A substitution in the non-coding 3' sequence, 123 bases downstream of the BRCA1-IRIS stop codon (IVS11+268C/A). The data indicates that it is probably a neutral change not associated with cancer risk. Our analysis suggests that the role of germ-line mutations at the specific BRCA1-IRIS sequence in breast cancer susceptibility, if any, is marginal and do not explain a significant fraction of high-risk breast/ovarian families, at least in the population analyzed.
authors.affiliation: Laboratory of Molecular Oncology, Hospital Clínico San Carlos, Madrid, Spain. delahoyam2002@yahoo.es
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Fernández
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez de Abajo
authors.forename: Alicia
authors.initials: A
authors.lastname: Tosar
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D012307:Risk Factors; D013030:Spain
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; D002868:Chromosomal Proteins, Non-Histone