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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

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

Authors: Quirinus JM Voorham, Jerry Janssen, Marianne Tijssen, Suzanne Snellenberg, Sandra Mongera, Nicole CT van Grieken, Heike Grabsch, Martin Kliment, Bjorn J Rembacken, Chris JJ Mulder, Manon van Engeland, Gerrit A Meijer, Renske DM Steenbergen, Beatriz Carvalho

Published in: BMC Cancer | Issue 1/2013

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Abstract

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.

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. 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 < 0.01). Combining both adenoma types, a positive trend between APC mutation and both WIF-1 and DKK3 methylation was observed (p < 0.05).

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.
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Metadata
Title
Promoter methylation of Wnt-antagonists in polypoid and nonpolypoid colorectal adenomas
Authors
Quirinus JM Voorham
Jerry Janssen
Marianne Tijssen
Suzanne Snellenberg
Sandra Mongera
Nicole CT van Grieken
Heike Grabsch
Martin Kliment
Bjorn J Rembacken
Chris JJ Mulder
Manon van Engeland
Gerrit A Meijer
Renske DM Steenbergen
Beatriz Carvalho
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-603

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