Evaluation of a Large, Population-Based Sample Supports a CpG Island Methylator Phenotype in Colon Cancer

摘要: Background & Aims: The concept of a CpG island methylator phenotype (CIMP), especially in microsatellite stable colon cancer, is not accepted universally. We therefore evaluated large population-based sample individuals with cancer and used univariate multivariate analyses CIMP clinicopathologic variables tumor mutations to determine the biologic relevance this phenotype. Methods: A total 864 tumors from Utah Northern California were by methylation-specific polymerase chain reaction islands hMLH1 , methylated (MINT) 1, MINT 2, 31, CDKN2A (p16) . high was defined as methylation at 2 or more these loci. BRAF V600E mutation determined sequencing. Microsatellite instability had been previously. Results: In analysis tumors, related significantly (odds ratio, 39.52; 95% confidence interval, 11.44–136.56), KRAS2 2.22; 1.48–3.34), older age ( P trend=.03), increased stage less likely be located distal .42; .27–.65). CIMP-high unstable also have mutation, proximally, occur (in analyses). However, than their counterparts wild type, TP53 poorly differentiated, proximally located, lower stages, (64.1% vs 17.6%). Conclusions: evaluation large, strongly supports cancer. presence absence has major effect on expression