Homozygous Deletions within 9p21-p22 Identify a Small Critical Region of Chromosomal Loss in Human Malignant Mesotheliomas

Previous DNA analyses have demonstrated that 9pl3-p22 is a frequent site of chromosomal loss in leukemia, glioma, melanoma, and lung and bladder carcinomas. Recent cytogenetic studies have revealed recurrent alterations 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 were identified in 19 (83%) cell lines. Homozygous losses (10 cell lines; 43%) occurred most often at the D9S171 and IFNA/IFNW loci. In 8 cell lines, 2 or more of the 9p loci examined were found to be homozygously lost; 2 others displayed homozygous losses only at the D9S171 locus. Results from our deletion mapping analysis suggest that D9S171 is located between IFNA/IFNW and D9SI26. The data presented here indicate that allelic loss from 9p21-p22 is a common occurrence in MM and further delineate the location of a putative 9p tumor suppressor gene(s) to a region between IFNA/IFNW and D9SI71. These MM cell lines may facilitate efforts to define an even smaller critically deleted region, leading to the eventual cloning and characterization of this gene.