Profiling CpG island field methylation in both morphologically normal and neoplastic human colonic mucosa

Belshaw, N J, Elliott, G O, Foxall, R. J., Dainty, J R, Pal, N, Coupe, A, Garg, D., Bradburn, D M, Mathers, John C. and Johnson, I T (2008) Profiling CpG island field methylation in both morphologically normal and neoplastic human colonic mucosa. British Journal of Cancer, 99 (1). pp. 136-142. ISSN 0007-0920

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Abstract

Aberrant CpG island (CGI) methylation occurs early in colorectal neoplasia. Quantitative methylation-specific PCR profiling applied to biopsies was used to quantify low levels of CGI methylation of 18 genes in the morphologically normal colonic mucosa of neoplasia-free subjects, adenomatous polyp patients, cancer patients and their tumours. Multivariate statistical analyses distinguished tumour from mucosa with a sensitivity of 78.9% and a specificity of 100% (P=3 × 10−7). In morphologically normal mucosa, age-dependent CGI methylation was observed for APC, AXIN2, DKK1, HPP1, N33, p16, SFRP1, SFRP2 and SFRP4 genes, and significant differences in CGI methylation levels were detected between groups. Multinomial logistic regression models based on the CGI methylation profiles from normal mucosa correctly identified 78.9% of cancer patients and 87.9% of non-cancer (neoplasia-free+polyp) patients (P=4.93 × 10−7) using APC, HPP1, p16, SFRP4, WIF1 and ESR1 methylation as the most informative variables. Similarly, CGI methylation of SFRP4, SFRP5 and WIF1 correctly identified 61.5% of polyp patients and 78.9% of neoplasia-free subjects (P=0.0167). The apparently normal mucosal field of patients presenting with neoplasia has evidently undergone significant epigenetic modification. Methylation of the genes selected by the models may play a role in the earliest stages of the development of colorectal neoplasia.

Item Type: Article
Faculty \ School:
Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:
Depositing User: Pure Connector
Date Deposited: 27 Feb 2018 11:30
Last Modified: 12 Jun 2020 23:49
URI: https://ueaeprints.uea.ac.uk/id/eprint/66383
DOI: 10.1038/sj.bjc.6604432

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