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 and Pilar Carvallo 1 1 Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile 2 Centro de Cancer, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile 3 Unidad de Patologia Mamaria, Hospital Base de Valdivia, Valdivia, Chile 4 Unidad de Patologia Mamaria, Hospital Barros Luco Trudeau, Santiago, Chile 5 Unidad de Patologia Mamaria, Hospital Regional de Antofagasta, Antofagasta, Chile 6 Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California, USA * These authors contributed equally to this work Correspondence to: Pilar Carvallo, email: pcarvallo@bio.puc.cl Keywords: BRCA1, BRCA2, founder mutation, breast cancer, Chile Received: April 28, 2017      Accepted: June 12, 2017      Published: June 29, 2017 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.