Nonrandom chromosome alterations in human malignant mesothelioma.
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.
Popescu
N C
NC
Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892.
Chahinian
A P
AP
DiPaolo
J A
JA
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000235:genetics*; D008875:Middle Aged; D011519:Proto-Oncogenes; D014407:Tumor Cells, Cultured