Evidence that DNA methylation imbalance is not involved in the development of malignant mesothelioma.
Methylation dysregulation has been a consistent finding in various malignancies, particularly those where the pathogenetic mechanisms are unclear. In order to test the hypothesis that methylation imbalance may not be a feature of cancers where the aetiologic agent or process is known, we studied the methylation status of the myogenic genes Myf-3 and Myf-4 by Southern blotting in malignant mesothelioma, a cancer strongly associated with asbestos exposure. DNA samples obtained from controls and mesothelioma patients did not exhibit hypermethylation of Myf-3 and hypomethylation of Myf-4, as noted in malignant lymphomas. The methylation status of Myf-3 and Myf-4 in malignant mesothelioma was similar to that of non-malignant cells indicating that dysregulation of the DNA methylating machinery may not be involved in mesothelioma development. The present findings do not support the view that methylation imbalance is a consequence of neoplastic transformation, but indicate that it may be one of the early molecular events involved in the genesis of some cancers.
Bagwe
A N
AN
Department of Pathology, University of Western Australia, Nedlands, Australia.
Kay
P H
PH
Spagnolo
D V
DV
D001194:Asbestos; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D006801:Humans; D008654:Mesothelioma / Q000235:genetics*; D017570:MyoD Protein / Q000235:genetics*; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D010997:Pleural Neoplasms / Q000235:genetics
D004273:DNA, Neoplasm; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; C063403:myogenic factor 6; D001194:Asbestos