Abstract B058: Germline mutation spectrum in hereditary cancer syndromes in a Latin American population
Authors: Sanabria-Salas María Carolina , Guevara Gonzalo , Rivera Ana Lucía , Huertas Antonio , Medina Vilma , Trujillo Lina María , Peña Esperanza , Wiesner Carolina 
Published: September 2020

Abstract
Introduction: Only 4% of the submissions to CLINVAR are from Latin American countries, similarly to Latino/Hispanic representation in other population genetic databases. We don’t know the spectrum of mutations affecting Colombian families with hereditary cancer syndromes; moreover, these cases are under diagnosed in our Country. We aimed to identify germline risk mutations in patients with a suspected hereditary cancer syndrome who were referred for genetic counseling at the largest cancer reference Institution in Colombia (INC-E.S.E.). Materials and methods: Descriptive cohort of patients referred to genetic counseling within the Hereditary Cancer Program at the INC-E.S.E. Germline genetic studies were performed on 147 individuals through NGS multi-gene panels and confirmed with Sanger sequencing or MLPA. Genetic results from more patients will be added to these statistics as those are being analyzed. Results: So far, results were obtained from 90 patients with a foreign company to study 83 genes, and 57 additional patients were studied at the INC-E.S.E., with a panel of 105 genes from Illumina in a MiSeq. Two bioinformatic pipelines (Illumina Variant Interpreter and SOPHIA Genetics) were used. Single Nucleotide Variants (SNVs), small insertions and deletions (INDELs), and Copy Number Variants (CNVs), were classified according to the ACMG criteria. Likely pathogenic or pathogenic mutations were identified in 22% of the patients (32/147). Of the total number of patients with an identified hereditary breast cancer syndrome (11/147, 7.48%), 6 are carriers of homologous repair genes mutation (3 in BRCA1, 1 in PALB2, 1 in CHEK2 and 1 in RAD51D); in BRCA1, one corresponds to the Colombian founder mutation A1708E and two carry the mutation BRCA1: c.1674delA (p.Gly559Valfs). The second most frequent was Lynch syndrome (8/147, 5.44%), 4 carry mutations in MLH1, 2 in PMS2, 1 in MSH6 and 1 in MSH2. It is interesting that 3/4 patients with mutations in MLH1 had the same splicing alteration (MLH1 c.790 + 1G&gt; A). Other 5 patients with a hereditary cancer syndrome were identified, including one of each: Li-Fraumeni, Multiple Endocrine Neoplasia type 1, Von Hippel Lindau, Neurofibromatosis 1 and MUTYH - Associated Polyposis (carrier of the two most frequent mutations in MUTYH; c.1187G&gt;A & c.536A&gt;G). Variants of Uncertain Significance (VUSs) were found in 47.62% and negative results in 32.65%. Conclusions: The finding of pathogenic mutations in 22% of this cohort is similar to what was previously reported for Colombia, but the percentage of VUSs is higher than other reports. Our lack of knowledge of the mutational spectrum in Colombians and our use of extensive multigene panels can explain this VUSs high rate.
Citation Format: María Carolina Sanabria-Salas, Gonzalo Guevara, Ana Lucía Rivera, Antonio Huertas, Vilma Medina, Lina María Trujillo, Esperanza Peña, Carolina Wiesner. Germline mutation spectrum in hereditary cancer syndromes in a Latin American population [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B058.