The CIMP phenotype in BRAF mutant serrated polyps from a prospective colonoscopy patient cohort

Fernando, Winnie C., Miranda, Mariska S., Worthley, Daniel L., Togashi, Kazutomo, Watters, Dianne J., Leggett, Barbara A. and Spring, Kevin J. (2014) The CIMP phenotype in BRAF mutant serrated polyps from a prospective colonoscopy patient cohort. Gastroenterology Research and Practice, 2014 . doi:10.1155/2014/374926

Author Fernando, Winnie C.
Miranda, Mariska S.
Worthley, Daniel L.
Togashi, Kazutomo
Watters, Dianne J.
Leggett, Barbara A.
Spring, Kevin J.
Title The CIMP phenotype in BRAF mutant serrated polyps from a prospective colonoscopy patient cohort
Journal name Gastroenterology Research and Practice   Check publisher's open access policy
ISSN 1687-6121
Publication date 2014-04-10
Year available 2014
Sub-type Article (original research)
DOI 10.1155/2014/374926
Open Access Status DOI
Volume 2014
Total pages 10
Place of publication New York, NY, United States
Publisher Hindawi Publishing Corporation
Language eng
Formatted abstract
Colorectal cancers arising via the serrated pathway are often associated with BRAF V600E mutation, CpG island methylator phenotype (CIMP), and microsatellite instability. Previous studies have shown a strong association between BRAF V600E mutation and serrated polyps. This study aims to evaluate CIMP status of all the serrated polyp subtypes and its association with functionally important genes such as MLH1, p16, and IGFBP7. CIMP status and methylation were evaluated using the real-time based MethyLight assay in 154 serrated polyps and 63 conventional adenomas. Results showed that CIMP-high serrated polyps were strongly associated with BRAF mutation and proximal colon. CIMP-high was uncommon in conventional adenomas (1.59%), occurred in 8.25% of hyperplastic polyps (HPs), and became common in sessile serrated adenomas (SSAs) (51.43%). MLH1 methylation was mainly observed in the proximal colon and was significantly associated with BRAF mutation and CIMP-high. The number of samples methylated for p16 and IGFBP7 was the highest in SSAs. The methylation panel we used to detect CIMP is highly specific for CIMP-high cancers. With this panel, we demonstrate that CIMP-high is much more common in SSAs than HPs. This suggests that CIMP-high correlates with increased risk of malignant transformation which was also observed in methylation of functionally important genes.
Keyword Island methylator phenotype
Colorectal cancer
Microsatellite instability
Hyperplastic polyps
DNA methylation
Colon cancer
Conventional adenomas
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article ID 374926

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
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