title: BRCA1 and BRCA2 mutations in a South American population.
abstract: A sample of 64 high-risk breast and/or ovarian cancer families from Chile were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIN no. 113705) and BRCA2 (MIN no. 600185) genes using conformation-sensitive gel electrophoresis, and the mutations found were confirmed with direct sequencing. Seven families (10.9%) were found to carry BRCA1 mutations and three families (4.7%) had BRCA2 mutations. Six different pathogenic mutations were detected in BRCA1, four that had been reported previously (c.187_188delAG; c.300T-->G, c.3450_3453delCAAG and IVS17-1G-->A) and two novel mutations (c.2605_2606delTT and c.4185_4188delCAAG). In BRCA2, we found three different pathogenic mutations, two previously described (c.6174delT and c.6503_6504delTT) and one novel mutation (c.5667delT). We also identified nine variants of unknown significance (five in BRCA1 and four in BRCA2). These findings indicate that the Chilean population has a heterogeneous spectrum of prevalent BRCA mutations. Given the results obtained in our study, the screening of the entire BRCA1 and BRCA2 coding regions is necessary for the molecular genetic testing of Chilean high-risk breast/ovarian cancer patients. To our knowledge, this is the first genetic study of BRCA gene mutations conducted in Chile. The Chilean population has a well-known admixed Amerindian-Caucasian ratio and, therefore, our findings are not only important per se, but they constitute the basis for improved and more specific genetic counselling, as well as to support for preventive campaigns geared toward the Chilean population.
authors.affiliation: Human Genetics Program, Institute of Biomedical Sciences, School of Medicine, University of Chile, Av. Independencia 1027, Casilla 70061, Santiago, Chile. ljara@med.uchile.cl
authors.forename: Lilian
authors.initials: L
authors.lastname: Jara
authors.forename: Sandra
authors.initials: S
authors.lastname: Ampuero
authors.forename: Eudocia
authors.initials: E
authors.lastname: Santibáñez
authors.forename: Lorena
authors.initials: L
authors.lastname: Seccia
authors.forename: Juan
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Mario
authors.initials: M
authors.lastname: Bustamante
authors.forename: Víctor
authors.initials: V
authors.lastname: Martínez
authors.forename: Alejandra
authors.initials: A
authors.lastname: Catenaccio
authors.forename: Guillermo
authors.initials: G
authors.lastname: Lay-Son
authors.forename: Rafael
authors.initials: R
authors.lastname: Blanco
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Reyes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002677:Chile / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005828:Genetics, Population; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm