Journal
EUROPEAN JOURNAL OF CANCER
Volume 44, Issue 17, Pages 2689-2695Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2008.09.004
Keywords
Colorectal cancer; Epigenetic events; Normal colonic tissue; Field cancerisation
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Funding
- Fundacion de Investigacion Medica Mutua Madrilena Automovilistica
- Fundacion Modica Aplicada
- Red Tematica de investigacion Cooperativa de Centros de Cancer (RTICCC) [C03/10]
- Fundacion Cientifica de la Asociacion Espanola contra el Cancer (AECC)
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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, p16(1NK4a), p15(1NK4b) and p14(ARF); 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 p16(1NK4a) 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. (C) 2008 Elsevier Ltd. All rights reserved.
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