Targetable gene fusions and aberrations in genitourinary oncology

Nat Rev Urol. 2020 Nov;17(11):613-625. doi: 10.1038/s41585-020-00379-4. Epub 2020 Oct 12.


Gene fusions result from either structural chromosomal rearrangement or aberrations caused by splicing or transcriptional readthrough. The precise and distinctive presence of fusion genes in neoplastic tissues and their involvement in multiple pathways central to cancer development, growth and survival make them promising targets for personalized therapy. In genitourinary malignancies, rearrangements involving the E26 transformation-specific family of transcription factors have emerged as very frequent alterations in prostate cancer, especially the TMPRSS2-ERG fusion. In renal malignancies, Xp11 and t(6;11) translocations are hallmarks of a distinct pathological group of tumours described as microphthalmia-associated transcription factor family translocation-associated renal cell carcinomas. Novel druggable fusion events have been recognized in genitourinary malignancies, leading to the activation of several clinical trials. For instance, ALK-rearranged renal cell carcinomas have shown responses to alectinib and crizotinib. Erdafitinib has been tested for the treatment of FGFR-rearranged bladder cancer. Other anti-fibroblast growth factor receptor 3 (FGFR3) compounds are showing promising results in the treatment of bladder cancer, including infigratinib and pemigatinib, and all are currently in clinical trials.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / therapy
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / therapy
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / therapy
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 6 / genetics
  • Chromosomes, Human, X / genetics
  • Gene Fusion
  • Gene Rearrangement*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / therapy
  • Male
  • Molecular Targeted Therapy*
  • Oncogene Fusion*
  • Oncogene Proteins, Fusion / genetics
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / therapy
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Translocation, Genetic*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / therapy
  • Urogenital Neoplasms / genetics*
  • Urogenital Neoplasms / therapy


  • Oncogene Proteins, Fusion
  • TMPRSS2-ERG fusion protein, human
  • Receptor, Fibroblast Growth Factor, Type 3