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ID 46628
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Author
Takeda, Masanori
Dong-Sheng, Sun
Oka, Tetsuhiro
Yamada, Eiji
Mori, Yoshiko
Shigeyasu, Kunitoshi
Morikawa, Tatsuya
Fujiwara, Toshiyoshi ORCID Kakenhi
Abstract
Secreted frizzled-related protein 2, (SFRP2) is a Wnt inhibitor whose promoter CpGs were recently found to be methylated at high frequency in colorectal cancers (CRCs). We hypothesized that the pattern of SFRP2 methylation may differ throughout the promoter during progressive tumorigenesis. Using combined bisulfite restriction analysis (COBRA), two methylation-sensitive regions (Regions A and B) of the SFRP2 promoter were investigated in 569 specimens of colorectal tissue:222 CRCs, 103 adenomatous polyps (APs), 208 normal colonic mucosa from CRC patients (N-Cs), and 36 normal colonic mucosa from subjects with no evidence of colorectal neoplasia at colonoscopy (N-Ns). Extensive (including both Regions A and B) and partial (either Region A or B) SFRP2 methylation levels were found in 61.7% and 24.8% of CRCs, 8.7% and 37.9% of APs, 3.9% and 39.9% of N-Cs, and 0% and 30.6% of N-Ns, respectively. Extensive methylation of the SFRP2 promoter was present primarily in CRCs, while partial methylation was common in APs. Whereas APs with the KRAS mutant showed no correlation to any pattern of SFRP2 methylation, extensive methylation of the SFRP2 promoter was significantly associated with KRAS mutant CRCs (p<.0001), suggesting that genetic alteration in the RAS-RAF pathway might precede the spread of CpG methylation through the SFRP2 promoter, which is observed in over 60% of advanced colorectal tumors.
Keywords
BRAF/KRAS mutations
promoter methylation
colorectal cancer
Amo Type
Original Article
Published Date
2011-06
Publication Title
Acta Medica Okayama
Volume
volume65
Issue
issue3
Publisher
Okayama University Medical School
Start Page
169
End Page
177
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
Copyright Holders
CopyrightⒸ 2011 by Okayama University Medical School
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publisher
Refereed
True
PubMed ID
Web of Sience KeyUT