Frequency of Deletions of EPCAM (TACSTD1) in MSH2-Associated Lynch Syndrome Cases

摘要: Lynch syndrome is an autosomal dominant cancer predisposition characterized by loss of function DNA mismatch repair enzyme MLH1, MSH2, MSH6, or PMS2. Mutations in MLH1 and MSH2 account for ∼80% the inherited cases. However, up to 20% cases suspected having a germline mutation due expression, not identified. Recent studies have shown that some are 3′ EPCAM/TACSTD1 deletions subsequently lead promoter hypermethylation. In this study, we examined frequency novel mechanism inactivation recruited through Colon Cancer Family Registry from Mayo Clinic Molecular Diagnostics Laboratory. From combined cohort, 58 were selected which immunohistochemical staining suggested but no mutations identified on follow-up testing. Of these cases, 11 demonstrated deletion EPCAM/TACSTD1. with deletion, methylation status was confirmed tumor tissue using methylation-sensitive PCR primers. One case showed hypermethylation absence detectable deletion. These results indicate approximately 25% detected, can be accounted data also suggest presence other alterations leading