Mutations in renal cell carcinoma

Urol Oncol. 2020 Oct;38(10):763-773. doi: 10.1016/j.urolonc.2018.10.027. Epub 2018 Nov 23.


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.

Keywords: Genetic mutations; Molecular genetics; Molecular profiling; Renal cell carcinoma; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Renal Cell / blood supply
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / therapy
  • Chemotherapy, Adjuvant / methods
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Genomics
  • Humans
  • Immunotherapy / methods
  • Kidney / pathology
  • Kidney / surgery
  • Kidney Neoplasms / blood supply
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / therapy
  • Molecular Targeted Therapy / methods
  • Mutation
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / prevention & control
  • Nephrectomy
  • Prognosis
  • Risk Assessment / methods
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use


  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Sirolimus