Malignant mesothelioma (MM) is a neoplasm closely associated with asbestos exposure, which has been implicated in 70–80% of the cases. In this study, nine MM (two fresh surgical specimens, two permanent cell lines, and five xenografts in nude mice) were examined cytogenetically. Six patients had a known history of asbestos exposure. Seven MM were chromosomally abnormal, the majority having complex structural alterations affecting different chromosomes, whereas two fresh surgical specimens had a normal chromosome constitution. Alterations of chromosome 3 were detected in seven cases and changes involving chromosomes 1 and 7 were observed in six cases. The breakpoints of translocations and deletions on chromosome 1 involved several bands; however, 50% of the breakpoints were near the locations of Blym, l-myc, and ski protooncogenes. Forty % of the breaks on chromosome 7 involved bands q11.1–11.2 and 20% were at q22, the location of the met protooncogene. Nonrandom changes on chromosome 3 were interstitial or terminal deletions, and translocations involving the region p14–21. The deleted 3p segment was identifiable as part of a chromosome translocation in one MM and was apparently lost in the other six. The deletions involving 3p are either spontaneous or asbestos-induced lesions at vulnerable genomic sites and are the most common and nonrandom chromosome alterations observed. Possibly 3p abnormalities are causally related to the development of this malignancy.
This investigation was supported in part by Grant CA 36283 awarded [to A.P.C.] by the National Cancer Institute, Department of Health and Human Services, Bethesda, MD 20892.