Mutations in renal cell carcinoma.
Renal cell carcinoma (RCC) is a commonly diagnosed and histologically diverse urologic malignancy. Clear cell RCC (ccRCC) is by far the most common, followed by the papillary and chromophobe subtypes. Sarcomatoid differentiation is a morphologic change that can be seen in all subtypes that typically portends a poor prognosis. In the past, treatment options for RCC were limited to cytokine-based therapy with a high-toxicity profile and low response rate. An increased understanding of the molecular basis of RCC has led to substantial improvement in treatment options in the form of targeted therapy and immunotherapy. A significant early discovery in RCC was frequent inactivation of the Von Hippel Lindau gene in ccRCC, which ultimately led to the development of vascular endothelial growth factor and mammalian target of rapamycin inhibitors. Further genomic sequencing of ccRCC tumors has identified other common mutations including BAP-1, PBRM1, SETD2, and PIK3CA. Many recent studies have explored how these mutations can affect prognosis and response to treatment. Likewise, papillary RCC has also been studied at the molecular level, which has shown a high level of mutations in the MET gene; early clinical data suggest the utility of MET targeted therapy. Finally, regarding the rarer sarcomatoid tumors, mutations in TP53 and NF2 may be important to their development. As we continue to learn more about what drives RCC at the molecular level, treatment options for RCC patients are diversifying.
["D'Avella|Christopher|C|", 'Abbosh|Phillip|P|', 'Pal|Sumanta K|SK|', 'Geynisman|Daniel M|DM|']
D020533:Angiogenesis Inhibitors D000074322:Antineoplastic Agents, Immunological D000971:Antineoplastic Combined Chemotherapy Protocols D014408:Biomarkers, Tumor D002292:Carcinoma, Renal Cell D017024:Chemotherapy, Adjuvant D004252:DNA Mutational Analysis D018572:Disease-Free Survival D023281:Genomics D006801:Humans D007167:Immunotherapy D007668:Kidney D007680:Kidney Neoplasms D058990:Molecular Targeted Therapy D009154:Mutation D009364:Neoplasm Recurrence, Local D009392:Nephrectomy D011379:Prognosis D018570:Risk Assessment D020123:Sirolimus
Renal cell carcinoma Targeted therapy Genetic mutations Molecular genetics Molecular profiling