Sporadic renal cell carcinoma: In studies performed to isolate and clone the tumor suppressor genes associated with initiation and progression of renal cell carcinoma (RCC) we have described DNA sequence deletions on the short arm of chromosome 3p in tumor tissue as well as tumor derived cell lines from 88% of patients with sporadic renal cell carcinoma and have localized the gene to the 3p21-26 region. In a study of tumor suppressor genes involved in progression of this malignancy we have described loss of heterozygosity at chromosomal loci of the Wilms tumor gene, the retinoblastoma gene, p53 gene and nm23. Familial renal cell carcinoma: In order to more precisely localize the disease gene for the familial form of RCC we have performed clinical evaluation and genetic linkage analysis on over 240 individuals from over 40 kindred with von Hippel-Lindau disease. We have localized the disease gene to the 3p26 locus. A prospective evaluation determined that preclinical DNA polymorphism analysis could accurately determine which individuals in this familial cancer syndrome carry the disease gene. Chromosomal walking as well as sequencing of CDNA probe candidate genes is currently underway. Prostate Carcinoma: We are evaluating the antitumor effect of a number of antineoplastic agents in human prostate carcinoma as well as evaluating tumor suppressor gene abnormalities in this malignancy. We have demonstrated that suramin has in vitro antitumor effects which are synergistic with other agents such as tumor necrosis factor. We participate in the clinical trials evaluating the antitumor effect of suramin in patients with advance prostate carcinoma and have initiated in vitro gene transfer studies to evaluate the role of tumor suppressor genes in initiation and progression of this malignancy. The significance of this project lies in the identification of the tumor suppressor genes associated with kidney cancer and prostate cancer as well as in the evaluation and development of antineoplastic agents for use in therapy of patients with advanced forms of these neoplasms.
