HOMOZYGOUS DELETIONS WITHIN 9P21-P22 IDENTIFY A SMALL CRITICAL REGIONOF CHROMOSOMAL LOSS IN HUMAN-MALIGNANT MESOTHELIOMAS

Previous DNA analyses have demonstrated that 9p13-p22 is a frequent si te of chromosomal loss in leukemia, glioma, melanoma, and lung and bla dder carcinomas. Recent cytogenetic studies have revealed recurrent al terations of 9p in malignant mesothelioma (MM). We have performed gene dosage studies of 23 MM cell lines, using probes for several 9p21-p22 loci (IFNB, IFNA/IFNW, D9S3, D9S126, D9S169, and D9S171), to identify a common region of deletion. Homozygous and/or hemizygous deletions w ere identified in 19 (83%) cell lines. Homozygous losses (10 cell line s; 43%) occurred most often at the D9S171 and IFNA/IFNW loci. In 8 cel l lines, 2 or more of the 9p loci examined were found to be homozygous ly lost; 2 others displayed homozygous losses only at the D9S171 locus . Results from our deletion mapping analysis suggest that D9S171 is lo cated between IFNA/IFNW and D9S126. The data presented here indicate t hat allelic loss from 9p21-p22 is a common occurrence in MM and furthe r delineate the location of a putative 9p tumor suppressor gene(s) to a region between IFNA/IFNW and D9S171. These MM cell lines may facilit ate efforts to define an even smaller critically deleted region, leadi ng to the eventual cloning and characterization of this gene.