Abstract 4164: Comprehensive analysis of germline variants in patients with hereditary breast and ovarian cancer susceptibility from 4 countries of Latin America

Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant disease mainly associated to high-risk pathogenic alleles in the BRCA1 and BRCA2 genes, but only in ~25% of HBOC cases. With the emergence of broader multi-gene panels, population-based studies have revealed that 3-4% of high-risk individuals have germline pathogenic variants in cancer risk genes other than BRCA1 and BRCA2, including ATM, CHEK2, PALB2, PTEN, TP53, and others. One of the understudied population with HBOC is the Latin American, and in this study, we aimed to identify the prevalence of high, moderate and new pathogenic alleles within two panels of cancer predisposition genes (143 and 86 genes) in 217 Latino breast cancer patients that met the NCCN criteria for panel testing in 4 countries. The Latino population was integrated by 68 Mexicans (31.3%), 19 Guatemalan (8.8%), 56 Argentinians (25.8%) and 74 Colombians (34.1%). We detected (i) 19.4% patients with pathogenic variants (42/217; Mexicans: 12, 5.5%; Guatemalans: 3, 1.4%; Argentinians: 10, 4.6%; Colombians: 17, 7.8%); (ii) 36.9% harbored variants with unknown clinical significance (VUS) (80/217; Mexicans: 24, 11.1%; Guatemalans: 6, 2.7%; Argentines: 26, 12%; Colombians: 24, 11.1%) and (iii) 43.7% were negative (95/217; Mexicans: 32, 14.7%; Guatemalans: 10, 4.6%; Argentines: 20, 9.2%; Colombians: 33, 15.2%). Moreover, most of the pathogenic variants (66%, 28/42) were found in high-risk genes including BRCA1/2, MSH2, MSH6 and PALB2. Our findings show the high locus heterogeneity of HBOC in the Latin American population. To establish the level of risk and the ultimate clinical utility of the variants detected in expanded panels tests, further international efforts are necessary in a population-based context. Citation Format: Felipe Vaca-Paniagua, Rosalia Quezada-Urban, Clara Estela Díaz Velásquez, Eva María Gómez García, Claudia Fabiola Méndez Catalá, Javier Oliver, Alejandra Franco, Cecilia Frecha, Cecilia Riggi, Claudia Carranza, Carlos Castañeda Altamirano, Ana Milena Gómez, Ana Lorena Montealegre, Sandra Gaitán Chaparro, Juan Javier López, Sandra Perdomo. Comprehensive analysis of germline variants in patients with hereditary breast and ovarian cancer susceptibility from 4 countries of Latin America [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4164.