Genetics and Tumor Microenvironment of Renal Cell Carcinoma

  • Sari Khaleel
  • Christopher Ricketts
  • W. Marston Linehan
  • Mark Ball
  • Brandon Manley
  • Samra Turajilic
  • James Brugarolas
  • Ari Hakimi
Keywords: renal cell carcinoma, clear cell carcinoma, non-clear cell renal cell carcinoma, genetics, tumor microenvironment


Renal cell carcinoma is a diverse group of diseases that can be distinguished by distinct histopathologic and genomic
features. In this comprehensive review, we highlight recent advancements in our understanding of the genetic and
microenvironmental hallmarks of kidney cancer. We begin with clear cell renal cell carcinoma (ccRCC), the most
common subtype of this disease. We review the chromosomal and genetic alterations that drive initiation and
progression of ccRCC, which has recently been shown to follow multiple highly conserved evolutionary trajectories
that in turn impact disease progression and prognosis. We also review the diverse genetic events that define the many
recently recognized rare subtypes within non-clear cell RCC. Finally, we discuss our evolving understanding of the
ccRCC microenvironment, which has been revolutionized by recent bulk and single-cell transcriptomic analyses,
suggesting potential biomarkers for guiding systemic therapy in the management of advanced ccRCC.

How to Cite
Khaleel, S., Ricketts, C., Linehan, W. M., Ball, M., Manley, B., Turajilic, S., Brugarolas, J., & Hakimi, A. (2022). Genetics and Tumor Microenvironment of Renal Cell Carcinoma. Société Internationale d’Urologie Journal, 3(6), 386-396.
2022 WUOF/SIU International Consultation on Urological Diseases