EVIDENCE THAT DNA METHYLATION IMBALANCE IS NOT INVOLVED IN THE DEVELOPMENT OF MALIGNANT MESOTHELIOMA

Methylation dysregulation has been a consistent finding in various mal ignancies, particularly those where the pathogenetic mechanisms are un clear In order to test the hypothesis that methylation imbalance may n ot be a feature of cancers where the aetiologic agent or process is kn own, we studied the methylation status of the myogenic genes Myf-3 and Myf-4 by Southern blotting in malignant mesothelioma, a cancer strong ly associated with asbestos exposure. DNA samples obtained from contro ls and mesothelioma patients did not exhibit hypermethylation of Myf-3 and hypomethylation of Myf-4, as noted in malignant lymphomas. The me thylation status of Myf-3 and Myf-4 in malignant mesothelioma was simi lar to that of non-malignant cells indicating that dysregulation of th e DNA methylating machinery may not be involved in mesothelioma develo pment. The present findings do nor support the view that methylation i mbalance is a consequence of neoplastic transformation, but indicate t hat it may be one of the early molecular events involved in the genesi s of some cancers.