Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype

• DOI: 10.1073/pnas.97.2.710
• Publication Date: 2002-07-26T14:35:07Z
• Authors: Minoru Toyota; Mutsumi Ohe-Toyota; Nita Ahuja; Jean-Pierre J. Issa
• Keywords: Microsatellite Instability; CpG site

Colorectal cancers (CRCs) are characterized by multiple genetic (mutations) and epigenetic (CpG island methylation) alterations, but it is not known whether these evolve independently through stochastic processes. We have recently described a novel pathway termed CpG methylator phenotype (CIMP) in CRC, which the simultaneous methylation of islands, including several genes, such as p16 , hMLH1 THBS1 . now studied mutations K-RAS p53 DPC4 TGFβRII panel colorectal tumors with or without CIMP. find that CIMP defines two groups significantly different lesions: frequent were found + CRCs (28/41, 68%) compared − cases (14/47, 30%, P = 0.0005). By contrast, 24% (10/41) vs. 60% (30/46) ( 0.002). Both differences independent microsatellite instability. These interactions between CIMP, mutations, preserved adenomas, suggesting they occur early carcinogenesis. The distinct combinations alterations each group suggest activation oncogenes inactivation tumor suppressor genes related to underlying mechanism generating molecular diversity cancer, rather than simply accumulate stochastically during cancer development.