Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas: DNA cytometry and comparative genomic hybridization of 90 cases

It is established that subtypes of human malignant mesotheliomas (MM) are associated with different survival times. Ninety cases of MM were examined using DNA cytometry and comparative genomic hybridization (CGH), with emphasis on the main histological subtypes; epithelioid, sarcomatoid and biphasic. A comparison by DNA cytometry revealed moderate differences, with the rare subgroup of mesodermomas having the highest and the sarcomatoid group the lowest rate of aneuploidy. Using CGH, 6.2 chromosomal imbalances per case on average could be detected. Losses (4.1/case) were more common than gains of chromosomal material (2.1/case). MM show no single, specific defect, but a typical pattern of genomic defects can be attributed to this tumour entity. Common losses are clustered at the chromosomal regions 9p21 (34%), 22q (32%), 4q31-32 (29%), 4p12-13 (25%), 14q12-24 (23%), 1p21 (21%), 13q13-14 (19%), 3p21, 6q22, 10p13-pter and 17p12-pter (16% each). Common gains are located on 8q22-23 (18%), 1q23/1q32 (16%), 7p14-15 and 15q22-25 (14% each). While differences in the frequencies of the defects between epithelioid and sarcomatoid MM are not as pronounced as are seen with the pleomorphic mesodermomas, several chromosomal locations (3p, 7q, 15q, 17p) show significant variations. The most pronounced distinguishing feature of sarcomatoid MM is a more than fourfold higher number of amplicons. These data indicate that MM has a distinctive tumour biology with a broad spectrum of heterogeneity, as reflected in morphology and also, more subtly, in the patterns of chromosomal imbalances of the subtypes.