Hereditary breast cancer (BC) syndromes corresponds to 10% - 15% of all cases diagnosed worldwide. Most of these cases are due to deleterious germline genetic variants in BRCA1/2 genes; nevertheless, multipanel testing have contribute to the identification of other risk genes, including other homologous recombination (HR) repair genes, such as PALB2, ATM, CHEK2 and RAD51D. Here we explore the mutation spectrum of Hereditary Breast and Ovarian Cancer (HBOC) Colombian cases as part of the Hereditary Cancer Program from the National Cancer Institute from Colombia, the largest reference cancer center in the country, that seeks to identified high risk families to offer preventive measures and screening recommendations. A total of 358 patients fulfilling criteria for HBOC have been so far analyzed with Next Generation Sequencing using a multigene panel. Overall, 47% have negative results and in the 33% we identified VUSs. In general, 20% have a pathogenic or potentially pathogenic genetic variant; from those, BRCA1 (n = 17) and BRCA2 (n = 17) were the most frequently mutated genes (47.2% among all positive results). Deleterious mutations in RAD51D and PALB2 (also important HR repair genes) were found in 7% and 5.6% of the cases tested. Interestingly, genotype:phenotype correlations were found for these genes, as breast cancer molecular subtypes were distributed differently depending on the gene affected. In concordance with other reports, triple negative breast cancers (TNBC) were more frequent in BRCA1 (9/17, 53%) and PALB2 (4/4, 100%) carriers, and luminal subtypes were more frequent in BRCA2 carriers (10/17, 59%). Mutations in RAD51D: c.94_95del (p.Val32Phefs*67) and PALB2: c.2288_2291del (p.Leu763Ter), were both recurrent mutations in our Colombian cases. Further haplotype analysis will help us to determine if mutation carriers shared a common ancestry. Citation Format: Maria Carolina Sanabria-Salas, Ana Lucía Rivera-Herrera, Ana Milena Gómez-Camargo, Luis G. Carvajal-Carmona, Martha Lucía Serrano-López. Recurrent germline mutations in RAD51D and PALB2 are present in Colombian hereditary breast and ovarian cancer families [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1211.

Hereditary colorectal cancer (CRC) syndromes accounts for approximately 5-10% of total CRC cases. Among those, Lynch syndrome (LS) is the most frequent, but the penetrance depends on the mismatch repair gene (MMR) affected. On the other hand, the Familial Adenomatous Polyposis (FAP) syndrome is less frequent, but with penetrance near to 100%. In Colombia we don't know the prevalence of these syndromes. In the National Cancer Institute from Colombia, the largest reference cancer center in the country, we aim to performed germline genetic analyses in Colombian CRC patients with a suspected hereditary cancer syndrome, as part of the Hereditary Cancer Program that seeks to identified high risk families to offer preventive measures and screening recommendations. A total of 66 patients with CRC fulfilling criteria have been so far analyzed with Next Generation Sequencing using a multigene panel. From those, the 32% have negative results, 41% have VUSs and 27% have positive results (meaning a pathogenic or potentially pathogenic genetic variant). The most prevalent CRC syndrome is Lynch (11/18, 61% with MMR mutated genes), followed by polyposis syndromes such as FAP (11% APC) and MAP (1.5% biallelic MUTYH). Most of our Lynch syndrome families fulfilled Bethesda or Amsterdam criteria. Two recurrent mutations in MLH1 were found in Lynch syndrome families (6/11, 54.5%), which are MLH1: c.1918C>T (p.Pro640Ser) and MLH1: c.790+1G>A. Further haplotype analysis will help us to determine if mutation carriers shared a common ancestry. Citation Format: Ana Lucía Rivera-Herrera, Ana Milena Gómez-Camargo, Martha Lucía Serrano-López, Luis G. Carvajal-Carmona, María Carolina Sanabria-Salas. Novel and recurrent germline mutations in Colombian families with colorectal cancer syndromes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2356.