Abstract# 1316: DNA methyltransferase-3B (DNMT3B) expression may contribute to CpG island methylator phenotype in colorectal cancer

Introduction: DNA methyltransferase-3B (DNMT3B) plays an important role in de novo CpG island methylation. Dnmt3b overexpression can induce colon tumor in mice, and methylation in various CpG islands in these mouse tumors are nonrandom, suggesting at least some specific targeting of Dnmt3b activity. We hypothesized that cellular DNMT3B level might influence the occurrence of widespread CpG island methylation (i.e., the CpG island methylator phenotype, CIMP) in colorectal cancer. In this study, we examined the relation between DNMT3B expression and CIMP in a large number of colorectal cancers. Materials and Methods: Utilizing 765 colorectal cancers from two cohort studies, we detected DNMT3B expression in 116 (15%) tumors by immunohistochemistry. Using real-time PCR (MethyLight), we quantified DNA methylation in 8 CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1 …