DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients

Wynter, Coral V. A., Kambara, Takeshi, Walsh, Michael D., Leggett, Barbara A., Young, Joanne and Jass, Jeremy R. (2006) DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients. International Journal of Cancer, 118 4: 907-915. doi:10.1002/ijc.21363


Author Wynter, Coral V. A.
Kambara, Takeshi
Walsh, Michael D.
Leggett, Barbara A.
Young, Joanne
Jass, Jeremy R.
Title DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
1097-0215
Publication date 2006-02-15
Year available 2005
Sub-type Article (original research)
DOI 10.1002/ijc.21363
Volume 118
Issue 4
Start page 907
End page 915
Total pages 9
Place of publication New York, NY, U.S.A.
Publisher Wiley-Liss
Language eng
Subject 1112 Oncology and Carcinogenesis
Formatted abstract
Colorectal adenomas have traditionally been regarded as homogeneous. The aim of our study was to identify molecular features that may differentiate sporadic adenomas from familial adenomas such as Familial Adenomatous Polyposis (FAP) and Multiple Adenoma patients. DNA methylation was tested at Methylated IN Tumor (MINT) loci (1,2,12,31) and the CpG promoter region of genes MLH1, HPP1, MGMT, p14ARF and p16INK4a in FAP-associated adenomas (33) from 5 patients with a known APC mutation (Group 1, FAP), adenomas (29) from 4 Multiple Adenoma patients (Group 2 Multiple), adenomas (14) from 3 patients with sporadic colorectal cancers showing high microsatellite instability (Group 3, MSI-H) and adenomas (16) from 7 patients, with sporadic colorectal cancers showing microsatellite stable or low level instability (Group 4, MSS/MSI-L). Aberrant Crypt Foci (ACFs), Hyperplastic Polyps (HPs) and cancers were also examined for methylation status as well as K-ras mutation. Multiple Adenoma patients were examined for germline polymorphisms in the base excision repair gene, MYH. The familial syndrome, FAP -associated adenomas showed a significantly low frequency of MINT methylation (15.5%,) compared to sporadic MSS/MSI-L-associated adenomas (35.5%). Group 3 (MSI-H) adenomas were different in that many showed serration and a high level of methylation (57.1%). Group 2, Multiple Adenoma cases, resembled sporadic MSS/MSI-L-associated adenomas. However the promoter regions of key genes, MGMT, p14ARF and p16INK4a were methylated to a greater extent than MINTs in both sporadic and familial adenomas. Genetic profiling of adenomas supports the concept that adenomas belonging to familial syndromes pursue a different pathway to tumorigenesis than their sporadic counterpar/ts from their earliest formation.
© 2005 Wiley-Liss, Inc.
Keyword Colorectal cancer
CpG methylation
Adenoma
FAP
Microsatellite instability
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Published online 8 September 2005 under "Cancer Ganetics"

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Thu, 08 Apr 2010, 08:44:38 EST by Jon Swabey on behalf of Faculty Of Health Sciences