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Nonrandom Chromosome Alterations in Human Malignant Mesothelioma¹

Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892, and Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, New York 10029

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.

¹ 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.

² To whom requests for reprints should be addressed.

Received 7/ 9/87. Revised 9/22/87. Accepted 9/28/87.

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