From Immunotherapy of Cancer to the Discovery of Kidney Cancer Genes: a Personal History (Colloquium Series on the Genetic Basis of Human Disease)

I had the good fortune to work at the National Cancer Institute from 1965 to 2005. The National Cancer Institute provided an environment that permitted my curiosity to flourish. Colleagues, particularly Marston Linehan, were essential to performance of the work. The work described in this manuscript was performed during a period of rapid advances in genetics. I was able to apply my clinical training and new genetic tools to study human kidney cancer. With the support of the National Cancer Institute, I was able to canvas physicians throughout the United States and Canada for referrals of families with multiple members affected with renal cancer. I was able to visit these families in their communities and determine the clinical and genetic features of their hereditary susceptibility to renal cancer, and to bring these families to Bethesda for comprehensive examinations. Using DNA analytic tools, we were able to identify several tumor suppressor genes that play major roles in the pathogenesis of human renal carcinoma thus opening up new fields for biochemical research into the pathogenesis of human renal carcinoma. Table of Contents: Introduction / From Immunotherapy of Cancer to Genetic Studies of Lung and Kidney Cancer / Preliminary Genetic Studies / von Hippel?Lindau Disease / Chromosome 3 Translocation Families / Hereditary Papillary Renal Carcinoma / The ?Open Door? Policy in the Urologic Oncology Clinic of the National Cancer Institute Birt-Hogg-Dube Syndrome / The Birt?Hogg?Dube Syndrome / Hereditary Leiomyoma Renal Cell Carcinoma / Succinate Dehydrogenase Gene Mutations and Renal Carcinoma / Tuberous Schlerosis and Renal Carcinoma / Affection Status and Linkage Analysis / Revisiting the National Cancer Institute Urologic Oncology Branch Collection of Renal Cancer Families to Identify Germline Mutations in Renal Carcinoma Genes in Previously Accessioned Families. Time between Family Accession and Germline Mutation Detection. Detection of Germline Mutations in Families with Single, Living Affected Individuals / Recent Discoveries in Human Renal Cancer Genetics / Use of Next-Generation DNA Sequencing to Study the Genetic Basis of Human Renal Cell Carcinomas / Conclusion / References