Association between CpG island methylation and microsatellite instability in colorectal cancer - PubMed (original) (raw)

. 1997 Aug 15;57(16):3370-4.

Affiliations

PMID: 9269998

Association between CpG island methylation and microsatellite instability in colorectal cancer

N Ahuja et al. Cancer Res. 1997.

Abstract

De novo methylation of promoter region CpG islands has been increasingly associated with transcriptional inactivation of important genes in neoplasia. To study the potential mechanisms underlying aberrant methylation in cancer, we have determined the methylation patterns of selected genes in colorectal cancers with and without microsatellite instability (MI), which results from defects in one of several base mismatch repair genes. A total of 47 colorectal cancers were analyzed, of which 15 were MI+ (32%). We now report that both the frequency and the extent of de novo methylation are strikingly increased in MI+ cancers. Hypermethylation of the p16 gene was found in 60% of MI+ cancers, compared to only 22% in MI- cancers (P = 0.02). Similarly, hypermethylation of the thrombospondin-1 (TSP-1) gene, an angiogenesis inhibitor, was increased in MI+ cancers (27% versus 0%; P = 0.008). Extensive methylation of insulin-like growth factor II (IGF2) and hypermethylated in cancer-1 (HIC-1) genes was observed in 60 and 80% of MI+ cancers, respectively, as contrasted with 6 and 38% of MI- cancers (P = 0.0002 and 0.01, respectively). Furthermore, 60% of the MI+ cancers displayed the hypermethylation events at two or more loci in a concordant manner compared to only 9% of the MI- cancers (P < 0.001). These results demonstrate a strong link between promoter hypermethylation and genetic instability due to deficient DNA repair.

PubMed Disclaimer

Cited by

Combined methylation of p16 and hMLH1 (CMETH2) discriminates a subpopulation with better prognosis in colorectal cancer patients with microsatellite instability tumors.
Veganzones S, Maestro ML, Rafael S, de la Orden V, Vidaurreta M, Mediero B, Espantaleón M, Cerdán J, Díaz-Rubio E. Veganzones S, et al. Tumour Biol. 2015 May;36(5):3853-61. doi: 10.1007/s13277-014-3027-1. Epub 2015 Jan 10. Tumour Biol. 2015. PMID: 25576161
Epigenetic phenotypes distinguish microsatellite-stable and -unstable colorectal cancers.
Kuismanen SA, Holmberg MT, Salovaara R, Schweizer P, Aaltonen LA, de La Chapelle A, Nyström-Lahti M, Peltomäki P. Kuismanen SA, et al. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12661-6. doi: 10.1073/pnas.96.22.12661. Proc Natl Acad Sci U S A. 1999. PMID: 10535979 Free PMC article.
Apoptosis and colorectal cancer.
Watson AJ. Watson AJ. Gut. 2004 Nov;53(11):1701-9. doi: 10.1136/gut.2004.052704. Gut. 2004. PMID: 15479695 Free PMC article. Review. No abstract available.
Aberrant p16((INK4a)) methylation is a frequent event in colorectal cancers: prognostic value and relation to mRNA expression and immunoreactivity.
Mitomi H, Fukui N, Tanaka N, Kanazawa H, Saito T, Matsuoka T, Yao T. Mitomi H, et al. J Cancer Res Clin Oncol. 2010 Feb;136(2):323-31. doi: 10.1007/s00432-009-0688-z. J Cancer Res Clin Oncol. 2010. PMID: 19779933
BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum.
Kambara T, Simms LA, Whitehall VL, Spring KJ, Wynter CV, Walsh MD, Barker MA, Arnold S, McGivern A, Matsubara N, Tanaka N, Higuchi T, Young J, Jass JR, Leggett BA. Kambara T, et al. Gut. 2004 Aug;53(8):1137-44. doi: 10.1136/gut.2003.037671. Gut. 2004. PMID: 15247181 Free PMC article.

Association between CpG island methylation and microsatellite instability in colorectal cancer - PubMed (original) (raw)