HOMOZYGOUS DELETIONS OF 9P21 IN PRIMARY HUMAN BLADDER-TUMORS DETECTEDBY COMPARATIVE MULTIPLEX POLYMERASE CHAIN-REACTION

Deletion mapping studies of primary bladder tumors have identified non overlapping areas of loss on each arm of chromosome 9, indicating that two distinct tumor suppressor loci are located on this chromosome. Th e deleted region on the p arm overlaps an area of 9p previously report ed to be lost in a variety of neoplasms. Detailed loss of heterozygosi ty analysis of 9p in 112 primary bladder tumors using 12 microsatellit e markers identified a minimal area of loss around the alpha-interfero n locus at 9p21-22. Frequent homozygous deletions of the alpha-interfe ron locus were then identified in these tumors by a novel, comparative , multiples polymerase chain reaction assay and were subsequently conf irmed by Southern analysis. Based on these deletions, a putative tumor suppressor gene locus involved in bladder tumorigenesis was localized to a 10 cM region (flanked by D9S162 and D9S171), previously implicat ed in the progression of many neoplasms. Application of the multiples polymerase chain reaction-based assay will allow rapid identification of homozygous deletions in many neoplasms and thus aid in mapping stud ies of critical suppressor genes.