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. 2017 Jun 29;8(43):74233-74243.
doi: 10.18632/oncotarget.18815. eCollection 2017 Sep 26.

BRCA1 and BRCA2 founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile

Carolina Alvarez  1 , Teresa Tapia  1 , Elisa Perez-Moreno  1 , Patricia Gajardo-Meneses  1 , Catalina Ruiz  2 , Mabel Rios  3 , Claudio Missarelli  3 , Mariela Silva  3 , Adolfo Cruz  4 , Luis Matamala  5 , Luis Carvajal-Carmona  6 , Mauricio Camus  2 , Pilar Carvallo  1
Affiliations

BRCA1 and BRCA2 founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile

Carolina Alvarez et al. Oncotarget. .

Abstract

Identifying founder mutations in BRCA1 and BRCA2 in specific populations constitute a valuable opportunity for genetic screening. Several studies from different populations have reported recurrent and/or founder mutations representing a relevant proportion of BRCA mutation carriers. In Latin America, only few founder mutations have been described. We screened 453 Chilean patients with hereditary breast cancer for mutations in BRCA1 and BRCA2. For recurrent mutations, we genotyped 11 microsatellite markers in BRCA1 and BRCA2 in order to determine a founder effect through haplotype analysis. We found a total of 25 mutations (6 novel) in 71 index patients among which, nine are present exclusively in Chilean patients. Our analysis revealed the presence of nine founder mutations, 4 in BRCA1 and 5 in BRCA2, shared by 2 to 10 unrelated families and spread in different regions of Chile. Our panel contains the highest amount of founder mutations until today and represents the highest percentage (78%) of BRCA1 and BRCA2 mutation carriers. We suggest that the dramatic reduction of Amerindian population due to smallpox and wars with Spanish conquerors, a scarce population increase during 300 years, and the geographic position of Chile constituted a favorable scenario to establish founder genetic markers in our population.

Keywords: BRCA1; BRCA2; Chile; breast cancer; founder mutation.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts to disclose.

Figures

Figure 1
Figure 1. Geographical distribution of recurrent mutations
A map of the Chilean territory indicating cities where patients were recruited is shown. Each mutation is represented with specific color, and each carrier family is indicated by a colored circle.
Figure 2
Figure 2
Minimum common haplotypes identified for each recurrent mutation in BRCA1 (A) and BRCA2 (B). Values under each STR marker indicate the size of the shared alleles. Scheme (bottom image) represents the localization of all markers and mutations in relation to each gene.
See this image and copyright information in PMC

References

    1. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266:66–71. - PubMed
    1. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G, Barfoot R, Hamoudi R, Patel S, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378:789–92. - PubMed
    1. Fackenthal JD, Olopade OI. Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer. 2007;7:937–48. - PubMed
    1. Jara L, Ampuero S, Santibáñez E, Seccia L, Rodríguez J, Bustamante M, Martínez V, Catenaccio A, Lay-Son G, Blanco R, Reyes JM. BRCA1 and BRCA2 mutations in a South American population. Cancer Genet Cytogenet. 2006;166:36–45. - PubMed
    1. Gallardo M, Silva A, Rubio L, Alvarez C, Torrealba C, Salinas M, Tapia T, Faundez P, Palma L, Riccio ME, Paredes H, Rodriguez M, Cruz A, et al. Incidence of BRCA1 and BRCA2 mutations in 54 Chilean families with breast/ovarian cancer, genotype-phenotype correlations. Breast Cancer Res Treat. 2006;95:81–87. - PubMed