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. 2008 Jul 8;99(1):136-42.
doi: 10.1038/sj.bjc.6604432. Epub 2008 Jun 10.

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

N J Belshaw  1 , G O Elliott, R J Foxall, J R Dainty, N Pal, A Coupe, D Garg, D M Bradburn, J C Mathers, I T Johnson
Affiliations

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

N J Belshaw et al. Br J Cancer. .

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 x 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 x 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.

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Figures

Figure 1
Figure 1
Differences in mean CGI methylation levels (±s.e.m.) in the apparently normal mucosa of males and females for MGMT (P=0.003), SFRP1 (P=0.003) and WIF1 (P=0.005). P-values were determined by ANOVA.
See this image and copyright information in PMC

References

    1. Al-Ghnaniem R, Peters J, Foresti R, Heaton N, Pufulete M (2007) Methylation of estrogen receptor alpha and mutL homolog 1 in normal colonic mucosa: association with folate and vitamin B-12 status in subjects with and without colorectal neoplasia. Am J Clin Nutr 86: 1064–1072 - PubMed
    1. Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6: 107–116 - PubMed
    1. Belshaw NJ, Elliott GO, Williams EA, Bradburn DM, Mills SJ, Mathers JC, Johnson IT (2004) Use of DNA from human stools to detect aberrant CpG island methylation of genes implicated in colorectal cancer. Cancer Epidemiol Biomarkers Prev 13: 1495–1501 - PubMed
    1. Belshaw NJ, Elliott GO, Williams EA, Mathers JC, Buckley L, Bahari B, Johnson IT (2005) Methylation of the ESR1 CpG island in the colorectal mucosa is an ‘all or nothing’ process in healthy human colon, and is accelerated by dietary folate supplementation in the mouse. Biochem Soc Trans 33: 709–711 - PubMed
    1. Byun T, Karimi M, Marsh JL, Milovanovic T, Lin F, Holcombe RF (2005) Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis. J Clin Pathol 58: 515–519 - PMC - PubMed

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