Expansion of CpG methylation in the SFRP2 promoter region during colorectal tumorigenesis.

摘要: 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 during progressive tumorigenesis. Using combined bisulfite restriction analysis (COBRA), two methylation-sensitive regions (Regions A and B) investigated 569 specimens tissue:222 CRCs, 103 adenomatous polyps (APs), 208 normal colonic mucosa from CRC patients (N-Cs), 36 subjects with no evidence neoplasia colonoscopy (N-Ns). Extensive (including both Regions partial (either Region or levels 61.7% 24.8% 8.7% 37.9% APs, 3.9% 39.9% N-Cs, 0% 30.6% N-Ns, respectively. was present primarily while common APs. Whereas APs KRAS mutant showed correlation any methylation, extensive significantly associated CRCs (p＜.0001), suggesting genetic alteration RAS-RAF pathway might precede spread CpG through promoter, which observed over 60% advanced tumors.