JaLCDOI 10.18926/AMO/46628
FullText URL 65_3_169.pdf
Author Takeda, Masanori| Nagasaka, Takeshi| Dong-Sheng, Sun| Nishie, Hiroyuki| Oka, Tetsuhiro| Yamada, Eiji| Mori, Yoshiko| Shigeyasu, Kunitoshi| Morikawa, Tatsuya| Mizobuchi, Satoshi| Fujiwara, Toshiyoshi|
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
File Version publisher
Refereed True
PubMed ID 21709714
Web of Science KeyUT 000292017500003