ROLE OF CHROMOSOME-9 IN HUMAN BLADDER-CANCER

The tumors of 20 patients with multifocal primary transitional cell ca rcinoma of the bladder or lymph node metastases were examined for mole cular genetic defects which we have previously found to be present in >50% of invasive tumors. These included loss of heterozygosity (LOH) o f chromosome 9, which occurs in superficial as well as invasive bladde r tumors, and LOH or chromosome 17p and p53 mutations, which are commo nly found only in invasive tumors. Analysis of multiple or recurrent p rimary tumors in 7 patients for these markers was generally consistent with recently published data that the tumors are monoclonal in origin and that p53 mutations occur as a late event in the generation of inv asive bladder cancers. Comparison of the primary tumors and metastases to regional lymph nodes in 14 patients demonstrated a complete concor dance between the molecular genetic defects present, showing that LOH of chromosomes 9 and 17p and p53 mutations occurred in the primary tum ors before metastasis. Because of the importance of chromosome 9 in bl adder cancer, we mapped the location of a putative tumor suppressor ge ne by restriction fragment length polymorphism analysis of 123 cases o btained in this and earlier studies. Most of the tumors showed LOH for more than one marker on chromosome 9. Results of mapping of 4 tumors with partial deletion of chromosome 9 suggests that the tumor suppress or gene is located between 9p12 and 9q34.1.