Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma

Aberrant promoter methylation and resultant silencing of several genes play s an important role in the pathogenesis of many tumor types. We compared th e methylation profile of 66 malignant mesotheliomas (MMs) and 40 lung adeno carcinomas using methylation-specific PCR for seven genes frequently methyl ated in lung cancer. We also compared the methylation frequencies of these genes as well as the methylation index, a reflection of all of the gene fre quencies, with the presence of SV40 large T-antigen (Tag) sequences, histol ogical subtype, and patient survival. Our major findings are: (a) with the exception of the RASSF1A promoter of the RASSF1 gene, frequencies of aberra nt methylation were significantly lower in MMs than in adenocarcinomas; (b) the frequency of RASSF1A aberrant methylation and the value of the methyla tion index were significantly higher in SV40 sequence positive MM than in n egative MM; and (c) the methylation index was higher in epithelial MM than in sarcomatous/mixed MM. Our results demonstrate a relationship between SV4 0 and aberrant methylation in MMs.