Methylation pattern of different regions of the MLH1 promoter and silencing of gene expression in hereditary and sporadic colorectal cancer.

摘要: Nonrandom, widespread promoter methylation of tumor suppressor genes is a common mechanism gene inactivation during tumorigenesis. We examined the status two distinct regions MLH1 (proximal and distal to transcription start site) expression by methylation-specific PCR immunohistochemistry. A total 72 colorectal tumors, both with (n = 51, 22 affected hereditary nonpolyposis cancer, HNPCC, defined according international clinical criteria 29 sporadic cases) without microsatellite instability (MSI) 21) were studied. Methylation was present in at least one 86% MSI cases, 33% cases lacking MSI, 23% HNPCC tumors. In known mutation 10) none methylated. Hypermethylation seen 45% vs. 5% MSI-negative 0% cases. The overall concordance between regarding good (P 0.009), but no significant correlation suppression immunohistochemical found. Our data confirm that hypermethylation are mutually exclusive mechanisms inducing mismatch repair deficiency support hypothesis as process evenly distributed along different promoter. © 2001 Wiley-Liss, Inc.