Recent advances in the molecular analysis of human malignant mesothelioma.

PURPOSE: To evaluate the role of asbestos, somatic genetic alterations, and simian virus 40 (SV40) in the formation of malignant mesothelioma (MM).
DESIGN: To review recent cytogenetic and molecular genetic advances in MM.
RESULTS: Exposure to asbestos is a major factor contributing to the development of most MMs. The accumulation of recurrent cytogenetic deletions in most MMs suggests a multistep process in this malignancy characterized by the loss and/or inactivation of multiple tumor suppressor genes (TSGs). Karyotypic, comparative genomic hybridization (CGH), and loss of heterozygosity (LOH) analyses of MMs have demonstrated frequent deletions of specific chromosomal regions within 1p, 3p, 6q, 9p, 13q, 15q, and 22q. Positional candidate gene approaches have identified TSGs within two of these regions, i.e., CDKN2A at 9p21 and NF2 at 22q12, which are frequently altered in MMs. In addition, recent studies have demonstrated the presence and expression of SV40 in many MMs. Proposed mechanisms by which asbestos and SV40 contribute to the development of MM are reviewed.
CONCLUSIONS: The identification of new TSGs involved in MM and understanding the role of these genes and of SV40 in the pathogenesis of this malignancy may lead to design of more effective therapeutic strategies.