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.
journal_name
Oncol Repjournal_title
Oncology reportsauthors
Menigatti M,Pedroni M,Verrone AM,Borghi F,Scarselli A,Benatti P,Losi L,Di Gregorio C,Schär P,Marra G,Ponz de Leon M,Roncucci Lsubject
Has Abstractpub_date
2007-06-01 00:00:00pages
1421-7issue
6eissn
1021-335Xissn
1791-2431journal_volume
17pub_type
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