O6-methylguanine-DNA methyltransferase promoter hypermethylation in colorectal carcinogenesis

Menigatti, Mirco and Pedroni, Monica and Verrone, Anna Maria and Borghi, Francesca and Scarselli, Alessandra and Benatti, Piero and Losi, Lorena and Di Gregorio, Carmela and Schär, Primo and Marra, Giancarlo and Ponz de Leon, Maurizio and Roncucci, Luca. (2007) O6-methylguanine-DNA methyltransferase promoter hypermethylation in colorectal carcinogenesis. Oncology reports, Vol. 17, no. 6. pp. 1421-1427.

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Official URL: http://edoc.unibas.ch/dok/A5253995

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Epigenetic alterations have been reported in colorectal neoplasia which can either complement or in some cases be predisposed to genetic alterations such as K-ras mutations. We examined the promoter methylation status of the CDKN2A and O6-methylguanine-DNA methyltransferase (MGMT) genes, after sodium bisulfite conversion and DNA amplification with methylation specific PCR. Moreover, we searched for G to A transitions in codons 12 and 13 of the K-ras oncogene in normal colorectal mucosae, aberrant crypt foci (ACF, early premalignant lesions) and carcinomas. CDKN2A hypermethylation was an infrequent event in ACF (2 of 26, 7.7%). On the contrary, MGMT hypermethylation was found in the normal mucosae (3 of the 12 samples, 25%), in 14 of the 26 ACF (53.8%) and in 7 of the 9 (77.8%) carcinomas examined. K-ras mutations were evident in 6 ACF (23%) and in 3 carcinomas (33.3%), mostly associated with MGMT promoter hypermethylation. These findings strongly support the hypothesis that epigenetic mechanisms play an important role in the early steps of colorectal carcinogenesis.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Molecular Genetics (Schär)
UniBasel Contributors:Schär, Primo Leo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:D.A. Spandidos
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:38

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