Promoter methylation of Wnt-antagonists in polypoid and nonpolypoid colorectal adenomas

作者：Voorham Quirinus J M; Janssen Jerry; Tijssen Marianne; Snellenberg Suzanne; Mongera Sandra; van Grieken Nicole C T; Grabsch Heike; Kliment Martin; Rembacken Bjorn J; Mulder Chris J J; van Engeland Manon; Meijer Gerrit A; Steenbergen Renske D M; Carvalho Beatriz^*

来源：BMC Cancer, 2013, 13: 603.

DOI：10.1186/1471-2407-13-603

• qMSP
• Colon
• Superficial elevated
• Flat adenoma
• CpG-island
• Epigenetic
• Hypermethylation
• Wnt-signaling pathway
• APC

Background: Nonpolypoid adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behaviour compared to their polypoid counterparts. A substantial proportion of nonpolypoid and polypoid adenomas lack APC mutations, APC methylation or chromosomal loss of the APC locus on chromosome 5q, suggesting the involvement of other Wnt-pathway genes. The present study investigated promoter methylation of several Wnt-pathway antagonists in both nonpolypoid and polypoid adenomas. %26lt;br%26gt;Methods: Quantitative methylation-specific PCR (qMSP) was used to evaluate methylation of four Wnt-antagonists, SFRP2, WIF-1, DKK3 and SOX17 in 18 normal colorectal mucosa samples, 9 colorectal cancer cell lines, 18 carcinomas, 44 nonpolypoid and 44 polypoid adenomas. %26lt;br%26gt;Results were integrated with previously obtained data on APC mutation, methylation and chromosome 5q status from the same samples. Results: Increased methylation of all genes was found in the majority of cell lines, adenomas and carcinomas compared to normal controls. WIF-1 and DKK3 showed a significantly lower level of methylation in nonpolypoid compared to polypoid adenomas (p %26lt; 0.01). Combining both adenoma types, a positive trend between APC mutation and both WIF-1 and DKK3 methylation was observed (p %26lt; 0.05). %26lt;br%26gt;Conclusions: Methylation of Wnt-pathway antagonists represents an additional mechanism of constitutive Wnt-pathway activation in colorectal adenomas. Current results further substantiate the existence of partially alternative Wnt-pathway disruption mechanisms in nonpolypoid compared to polypoid adenomas, in line with previous observations.

• 出版日期2013-12-19