Recurring loss involving chromosomes 1, 3, and 22 in malignant mesothelioma: possible sites of tumor suppressor genes

Cytogenetic analysis was performed on short-term cultures of primary tumor tissue obtained from five patients with pleural malignant mesothelioma. Clonal karyotypic abnormalities were detected in four patients, none of whom had received cytotoxic therapy prior to karyotypic evaluation. Recurring chromosomal changes included partial deletions of 1p and 3p, and monosomy of 18, 19, and 22. We also reviewed data on 24 previously reported pretreatment patients and determined that alterations of chromosomes 1, 3, and 22 are frequently associated with malignant mesothelioma. Partial loss of chromosome 1 due to deletions or other rearrangements most frequently involve bands 1p11-pter with the shortest region of overlap (SRO) occurring at 1p21-p22 in our patients. Deletions and other structural changes of chromosome 3 usually involve the region 3p14-p25. The SRO of 3p deletions appeared to be at band 3p21. Monosomy 22 represents the most consistent specific whole chromosome loss seen in malignant mesothelioma, being observed in 11 of 28 cases summarized. In addition, structural changes of 22q have been observed in three patients, and a breakpoint at 22q11 was reported in each case. Taken collectively, these data suggest that a cascade of events involving alterations of genes on more than one specific chromosome may play a critical role in the development of malignant mesothelioma. The pattern of recurring chromosomal loss, particularly of 1p, 3p, and 22q, indicates that these regions should be targeted for future molecular investigations into the possible involvement of suppressor genes in this malignancy.