title: Spectrum of BRCA1/2 point mutations and genomic rearrangements in high-risk breast/ovarian cancer Chilean families.
abstract: The distribution of BRCA1/2 germline mutations in breast/ovarian cancer (BC/OC) families varies among different populations. In the Chilean population, there are only two reports of mutation analysis of BRCA1/2, and these included a low number of BC and/or OC patients. Moreover, the prevalence of BRCA1/2 genomic rearrangements in Chilean and in other South American populations is unknown. In this article, we present the mutation-detection data corresponding to a set of 326 high-risk families analyzed by conformation-sensitive gel electrophoresis and heteroduplex analysis. To determine the contribution of BRCA1/2 LGRs in Chilean BC patients, we analyzed 56 high-risk subjects with no pathogenic BRCA1/2 point mutations. Germline BRCA1/2 point mutations were found in 23 (7.1%) of the 326 Chilean families. Families which had at least three BC and/or OC cases showed the highest frequency of mutations (15.9%). We identified 14 point pathogenic mutations. Three recurrent mutations in BRCA1 (c.187_188delAG, c.2605_2606delTT, and c.3450_3453delCAAG) and three in BRCA2 (c.4969_4970insTG, c.5374_5377delTATG, and c.6503_6504delTT) contributed to 63.6 and 66.7% of all the deleterious mutations of each gene, which may reflect the presence of region-specific founder effects. Taken together BRCA1/2 recurrent point mutations account for 65.2% (15/23) of the BRCA1/2 (+) families. No large deletions or duplications involving BRCA1/2 were identified in a subgroup of 56 index cases negative for BRCA1/2 point mutations. Our study, which is the largest conducted to date in a South American population, provides a comprehensive analysis on the type and distribution of BRCA1/2 mutations and allelic variants.
authors.affiliation: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, PO Box 70061, Santiago, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Gonzalez-Hormazabal
authors.forename: Sara
authors.initials: S
authors.lastname: Gutierrez-Enriquez
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaete
authors.forename: Jose M
authors.initials: JM
authors.lastname: Reyes
authors.forename: Octavio
authors.initials: O
authors.lastname: Peralta
authors.forename: Enrique
authors.initials: E
authors.lastname: Waugh
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez
authors.forename: Sonia
authors.initials: S
authors.lastname: Margarit
authors.forename: Teresa
authors.initials: T
authors.lastname: Bravo
authors.forename: Rafael
authors.initials: R
authors.lastname: Blanco
authors.forename: Orland
authors.initials: O
authors.lastname: Diez
authors.forename: Lilian
authors.initials: L
authors.lastname: Jara
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics*; D002677:Chile; D005091:Exons; D005192:Family Health; D005260:Female; D018703:Founder Effect; D015321:Gene Rearrangement; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D017354:Point Mutation; D012306:Risk