Abstract 18: Molecular characterization of Brazilian patients suspected for Lynch syndrome

Abstract

Abstract Lynch syndrome (LS), former known as Hereditary Non Polyposis Colorectal cancer (HNPCC), accounts for 3-5% of all colorectal cancers (CRC) and is inherited in an autossomal dominant fashion. This syndrome is characterized by early CRC onset, high incidence of tumors in the ascending colon, excess of synchronous and metachronous tumors, and accelerated transition adenoma-carcinoma (2-3 years). Nowadays, LS is regarded of patients who carry deleterious germline mutations in one of the five Mismatch repair genes, such as MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), post-meiotic segregation increased 1 (PMS1) or post-meiotic segregation increased 2 (PMS2). In order to characterize Brazilian patients suspect for LS, we assessed the frequency of germline point mutations in MSH6, PMS1 and PMS2 in patients negative for point mutations in MLH1 and MSH2 by capillary sequencing. We also assessed chromosomal deletions in MLH1 and MSH2 and MSH6 generating a complete characterization of MMR genes. The analysis of the five MMR genes revealed 46 carriers of pathogenic mutations, including 25 in MSH2 (54%), 16 in MLH1 (35%), 4 in MSH6 (9%) and one in PMS2 (2%) gene In addition, from the 70 negative patients, we selected one mutation negative family that met the stringent Amsterdam criteria (AC) for whole exome sequencing using the SOLID platform. For this family, we selected 5 close blood relatives, including 3 affected and 2 unaffected individuals in order to facilitate the identification of new susceptibility genes with autosomal dominant pattern. The results revealed two candidate genes, c-KIT and WDR27 that segregated with the disease. Additional analysis are under evaluation. Citation Format: Felipe C. Silva, Giovana T. Torrezan, Márcia CP Figueiredo, Jose Roberto O. Ferreira, Érika M. Santos, Wilson T. Nakagawa, Samuel Aguiar-Junior, Benedito M. Rossi, Fabio O. Ferreira, Dirce M. Carraro. Molecular characterization of Brazilian patients suspected for Lynch syndrome. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 18. doi:10.1158/1538-7445.CANSUSC14-18