Epigenetic events in normal colonic mucosa surrounding colorectal cancer lesions

Abstract Gene inactivation by promoter hypermethylation has been demonstrated in the colonic mucosa of colorectal cancer (CRC) patients. However, current data do not prove direct involvement of this epigenetic modification in the early stages of CRC. Promoter methylation profiles of E-cadherin , hML...

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Bibliographic Details
Published in:European journal of cancer (1990) 2008-11, Vol.44 (17), p.2689-2695
Main Authors: Ramírez, N, Bandrés, E, Navarro, A, Pons, A, Jansa, S, Moreno, I, Martínez-Rodenas, F, Zárate, R, Bitarte, N, Monzó, M, García-Foncillas, J
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Cell Transformation, Neoplastic - genetics
Colorectal cancer
Colorectal Neoplasms - genetics
DNA Methylation - genetics
Epigenesis, Genetic
Epigenetic events
Female
Field cancerisation
Genes, Neoplasm - genetics
Genes, p53 - genetics
Genes, ras - genetics
Hematology, Oncology and Palliative Medicine
Humans
Intestinal Mucosa
Lymphatic Metastasis
Male
Medical sciences
Microsatellite Repeats - genetics
Middle Aged
Mutation - genetics
Normal colonic tissue
Pharmacology. Drug treatments
Promoter Regions, Genetic - genetics
Proto-Oncogene Proteins B-raf - genetics
Tumors
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Summary:Abstract Gene inactivation by promoter hypermethylation has been demonstrated in the colonic mucosa of colorectal cancer (CRC) patients. However, current data do not prove direct involvement of this epigenetic modification in the early stages of CRC. Promoter methylation profiles of E-cadherin , hMLH1 , MGMT , p16INK4a , p15INK4b and p14ARF ; mutations of K-ras , B-raf and TP53 and microsatellite instability (MSI) were examined in normal and cancerous colonic mucosal tissue in 82 CRC patients using methylation-specific PCR assays. Methylation of hMLH1 and MGMT in normal mucosa correlated significantly with MSI and K-ras activation in neighbouring cancerous mucosal tissues. Similarly, poorly differentiated tumours were associated with methylated p16INK4a and E-cadherin in neighbouring normal colonic tissues (NCTs). Our results indicate that epigenetic changes in mucosa surrounding colorectal neoplastic lesions may describe a ‘field cancerisation’ phenomenon that may occur previous to genetic alterations in early stages of carcinogenesis.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2008.09.004