The long-term goal of our proposal is to improve the health of men diagnosed with renal cell carcinoma (RCC). To this end, we seek to understand the underlying molecular basis of recurrence and/or mortality following radical nephrectomy for RCC. Kidney cancer is one of the most common tumors worldwide, and the clinical trajectory of kidney cancer is extremely variable even within existing categories of risk. Current methods for risk stratification rely almost solely on tumor stage and grade and are used to drive the investigation of adjuvant therapies, including tyrosine kinase inhibitors (TKI) in high risk patients. Unlike for other tumor types (e.g., breast cancer, lung cancer, etc.), no comprehensive molecular assays are available to augment clinical decision-making for patients with kidney cancer after surgical removal. Recent exomic and transcriptomic profiling of diverse kidney cancer subtypes has begun to define the common molecular alterations in RCC and nominate potential DNA and RNA biomarkers that may be clinically useful. There is a pressing need for new ancillary studies to help guide the clinical management of patients with kidney cancer. Given recent advances in molecular profiling, a clear opportunity exists to leverage our emerging understanding of the molecular pathogenesis of kidney cancer to develop novel molecular biomarker assays. Our international research team, composed of experts in kidney cancer management and genomics, coupled with our distinctive and extensive access to relevant tissue resources, is uniquely poised to complete our stated research plan.