Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability

摘要: Recent studies have demonstrated the presence of microsatellite instability (MSI) in tumors from patients with hereditary nonpolyposis colon cancer and a subset sporadic colorectal (CRC). In CRC, three tumor phenotypes been defined: stable (MSS), low-frequency MSI, high-frequency MSI (MSI-H). Although defective mismatch repair, consisting primarily alterations hMSH2 hMLH1, is believed to be responsible for phenotype majority cancer, genetic defect this CRC has yet clearly delineated. Somatic or germ-line these two genes identified only minority cases. Analysis protein expression patterns hMLH1 unselected however, suggests that may account MSI-H an effort explore underlying molecular basis findings, we examined methylation status presumptive hMLHI promoter region 31 vary regard their (MSI-H MSS), (MLH- MLH+), gene mutation (Mut+ Mut-) status. Hypermethylation occurred all 13 MSI-H/ MLH- did not detectable within gene. Of those containing somatic (n = 7, including 3 frameshift, 1 nonsense, 2 missense mutations, multiple mutations: missense, splice-site alteration, frameshift), four had normal pattern, whereas others hypermethylation region. Two cases other frameshift alteration. The single MSI-H/Mut+ expression, as well 9 10 MSS cases, lacked promoter. was observed any These results suggest principal mechanism inactivation characterized by widespread MSI.