We are studying the molecular genetics of renal cell carcinoma, evaluating growth factor production by genitourinary tumors and participating in studies of adoptive immunotherapy in patients with advanced malignancies. In collaboration with Berton Zbar we tested by the molecular technique of restriction fragment polymorphism analysis for a DNA sequence deletion in the short arm of chromosome 3 in both neoplastic and somatic tissue in patients with sporadic renal cell carcinoma. We found loss of alleles at loci in the short arm of chromosome 3 in all 11 of the patients who could be evaluated. We also tested for gene loss at chromosome 11 and 15 and found no evidence for a generalized reduction to homozygosity. Loss of specific gene products from somatic cells may be critical in the origin or evolution of renal cell carcinoma and suggest that a recessive oncogene may be involved in tumorogenesis. Studies are in progress to analyze by RFLP analysis more pairs in somatic tissue, to analyze metastatic tissue for gene deletion and to further characterize possible gene deletions at other chromosomal sites. Other collaborative studies to further characterize the area of DNA deletion and to introduce a nondeleted chromosome 3 into renal cell carcinoma are underway. We have demonstrated that tumor necrosis factor stimulates bone resorption and that it does so in a hormone-like fashion and that prostate carcinoma produces a factor which stimulates bone resorption in a transforming growth factor-like fashion. We have evaluated patients with metastatic and locally advanced renal cell carcinoma prior to entry into therapy with adoptive immunotherapy and have performed over 40 radical nephrectomies in the last two years in patients with renal cell carcinoma as part of this protocol and in support of basic and clinical studies of tumor infiltrating lymphocytes. We have also characterized the renal toxicity in patients treated with Interleukin-2, which is a major dose-limiting aspect to this therapy.
