Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma.

The relationship of molecular abnormalities with clinicopathologic features and survival in colorectal signet ring cell carcinoma, and its comparison with mucinous and conventional adenocarcinomas, has not been well studied. High-level microsatellite instability, loss of heterozygosity (LOH) at four loci, CpG island methylation phenotype based on seven loci, BRAF V600E mutation and KRAS mutation in signet ring cell carcinoma were compared with mucinous and conventional adenocarcinomas. The relationship of these molecular features in signet ring cell carcinoma with clinicopathologic features and survival was examined.

MUC2 gene promoter methylation in mucinous and non-mucinous colorectal cancer tissues.

Abundant mucin production and MUC2 expression is the key feature of mucinous colorectal cancer (CRC). Although MUC2 gene methylation has been thought to play an important role in loss of MUC2 expression, the tissues are difficult to analyze because of the cellular heterogeneity of tissue samples. In the present study, we determined the role of region-specific methylation in the MUC2 promoter in MUC2 expression in CRC.

Distinct CpG island methylation profiles and BRAF mutation status in serrated and adenomatous colorectal polyps.

A subset of colorectal cancers with CpG island methylator phenotype-high (CIMP-H) is frequently associated with MSI and BRAF V600E mutation. Since limited data are available on different histological types of colorectal polyps, we compared the pattern and the frequency of promoter methylation, CIMP-H, MSI, KRAS and BRAF V600E mutations and the relationship among these molecular parameters and the clinicopathologic characteristics in 110 serrated polyps (48 hyperplastic polyps, 32 sessile serrated adenomas and 30 serrated adenomas) and 32 tubular adenomas using 7 commonly used tumor-associated gene loci. No significant difference in the frequency of overall methylation frequency (86% vs.

CpG island methylation is frequently present in tubulovillous and villous adenomas and correlates with size, site, and villous component.

CpG island methylator phenotype (CIMP) pathway in colorectal cancer is characterized by methylation of promoter regions of multiple putative tumor suppressor genes. Aberrant methylation also occurs in serrated and adenomatous polyps. We examined 32 tubulovillous/villous adenomas and 30 tubular adenomas for BRAF/KRAS mutations and methylation at hMLH1, p16, HIC1, RASSF2, MGMT, MINT1, and MINT31.