Developing study designs that focus on stratified samples (by VHL and/or HIF1A/HIF2A status) along with multiple samples from tumors and a multi-domain approach (such as proteotranscriptomic) is necessary to more clearly define the molecular pathogenesis of ccRCC and identify new therapeutic targets that are required for metastatic ccRCC. The gene discussed is HIF1A; the disease is nonpapillary renal cell carcinoma.