RESUMEN
INTRODUCTION: Lynch syndrome (LS) is an autosomal dominant disorder characterized by early age of onset and increased risk of developing extracolonic tumors. Molecular diagnosis of LS requires identification of germline mutations in one of the Mismatch Repair (MMR) genes. AIM: The objective of the study was to investigate the prevalence of MLH1/MSH2 mutation carriers among Moroccan patients with colorectal cancer (CRC) in a hospital-based cohort. METHODS: In this study, 214 CRC patients from COLORECFez cohort were included. Patients whose tumors showed MMR deficiency (MMR-D) and wild-type BRAF were selected to undergo mutational analysis of the MLH1 and MSH2 genes using Sanger sequencing. RESULTS: A total of 24 MMR-D tumors were identified (11.2%) among 214 CRC tested for MMR protein expression. The BRAF p.Val600Glu mutation was absent in all tumors deficient for MLH1 protein. Molecular screening showed germline MMR mutations (MLH1/MSH2) in four cases, two of which fulfilled Amsterdam criteria II and two met at least one of the revised Bethesda guidelines. The estimated frequency of MLH1/MSH2 mutations in Moroccan CRC patients was 1.87%. CONCLUSIONS: The present study reports a relatively high incidence of MLH1/MSH2 (1.87%). These results confirm the contribution of MMR genes to CRC susceptibility in our population and provide evidence regarding the requirement of implementing a national screening program for LS in Morocco.