title: Distinct CpG island methylation profiles and BRAF mutation status in serrated and adenomatous colorectal polyps.
abstract: 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. 100%) and CIMP-H (39% vs. 28%) between serrated polyps and tubular adenomas was observed, but proximally located serrated polyps showed more frequent methylation at 5 of 7 loci examined, and were more likely to be CIMP-H (62% vs. 22%). MGMT methylation was more common in tubular adenomas while MLH1 and HIC1 were more frequently methylated in serrated polyps. BRAF mutation was frequently present in all types of serrated polyps (80%), but was absent in tubular adenomas and was not associated with CIMP or MSI status. These results show comparable frequencies of promoter methylation of tumor-associated genes and CIMP-H, but distinct differences in gene-specific or colonic site-specific methylation profiles occur in serrated polyps and tubular adenomas. BRAF mutation occurs independently of CIMP and MSI in all types of serrated polyps and may serve as a marker of serrated pathway of colorectal carcinogenesis.
authors.affiliation: Gastrointestinal Research Laboratory (151M2), Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kakar
authors.forename: Lisa
authors.initials: L
authors.lastname: Cun
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.forename: Young S
authors.initials: YS
authors.lastname: Kim
mesh_terms: D018256:Adenomatous Polyps / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018899:CpG Islands; D019175:DNA Methylation; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins