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.

O6-methylguanine-DNA methyltransferase promoter hypermethylation in colorectal carcinogenesis / Menigatti, Mirco; Pedroni, Monica; Verrone, Am; Borghi, F; Scarselli, A; Benatti, Piero; Losi, L; Di Gregorio, C; Schär, P; Marra, G; PONZ DE LEON, Maurizio; Roncucci, Luca. - In: ONCOLOGY REPORTS. - ISSN 1021-335X. - STAMPA. - 17:6(2007), pp. 1421-1427. [10.3892/or.17.6.1421]

O6-methylguanine-DNA methyltransferase promoter hypermethylation in colorectal carcinogenesis

MENIGATTI, Mirco;PEDRONI, Monica;BENATTI, Piero;Losi L;PONZ DE LEON, Maurizio;RONCUCCI, Luca
2007

Abstract

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.
2007
17
6
1421
1427
O6-methylguanine-DNA methyltransferase promoter hypermethylation in colorectal carcinogenesis / Menigatti, Mirco; Pedroni, Monica; Verrone, Am; Borghi, F; Scarselli, A; Benatti, Piero; Losi, L; Di Gregorio, C; Schär, P; Marra, G; PONZ DE LEON, Maurizio; Roncucci, Luca. - In: ONCOLOGY REPORTS. - ISSN 1021-335X. - STAMPA. - 17:6(2007), pp. 1421-1427. [10.3892/or.17.6.1421]
Menigatti, Mirco; Pedroni, Monica; Verrone, Am; Borghi, F; Scarselli, A; Benatti, Piero; Losi, L; Di Gregorio, C; Schär, P; Marra, G; PONZ DE LEON, Ma...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/845707
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