Deletions of chromosome 4 at multiple sites are frequent in malignant mesothelioma and small cell lung carcinoma

Recent allelotyping studies suggest that allelic losses at one or both arms of chromosome 4 are frequent in several tumor types. Cytogenetic studies o f malignant mesothelioma (MM) and comparative genomic hybridization analyse s of small cell lung carcinoma (SCLC) suggest that chromosome 4 deletions m ay also play a role in these tumor types, although these results have not b een confirmed bg allelotyping. In an effort to more precisely identify and map the locations of putative tumor suppressor gene(s) on chromosome 4 invo lved in the pathogenesis of these tumors, we performed loss of heterozygosi ty studies using 16 polymorphic microsatellite markers. After precise micro dissection of archival surgical cases, me studied DNA obtained from 20 MMs, 21 SCLCs, and 20 non-SCLCs (NSCLCs), In addition, DNA from 14 SCLC and 17 NSCLC cell lines and corresponding B lymphoblastoid lines were studied, In MM and SCLC, we observed frequent losses at three nonoverlapping regions: ( a) 4q33-34 (region R1; >80%); (b) 4q25-26 (region R2; >60%); and (c) 4p15.1 -15.3 (region R3; >50%). Losses at these sites occurred at lower frequencie s in NSCLC (>20-30%), Data from tumors and cell lines were similar. In MM a nd SCLC, the most frequently observed pattern was loss at all three regions . However, in NSCLC, the most frequent pattern was loss at R3 alone. Our st udy has delineated three nonoverlapping regions of frequent deletions on ch romosome 4 in MM and SCLC, suggesting that there may be three putative supp ressor genes on chromosome 4, the inactivation of which may be important in the pathogenesis of these tumor types.