Genetic Differences Between Bladder and Upper Urinary Tract Carcinoma: Implications for Therapy

John P. Sfakianos, Zeynep Gul, Shahrokh F. Shariat, Surena F. Matin, Siamak Daneshmand, Elizabeth Plimack, Seth Lerner, Morgan Roupret, Sumanta Pal

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

CONTEXT: Bladder urothelial carcinoma (BUC) and upper tract urothelial carcinoma (UTUC) have genetic differences, which may influence therapy. OBJECTIVE: The aim of the current review was to summarize the current genetic understanding of upper tract and BUC. EVIDENCE ACQUISITION: PubMed, Cochrane, and Web of Science online databases were searched systematically up to February 2020, using the following keywords: urothelial carcinomas, upper urinary tract, renal pelvis, ureter, bladder cancer, and genetics. EVIDENCE SYNTHESIS: UTUC and BUC share mutations in similar genes, such as FGFR3, TP53, and HRAS, and epigenetic genes, such as KDM6A and KMT2A-C, but at varying frequencies. Furthermore, subtyping of UTUC and BUC has identified similar expression subtypes, but UTUC is more often luminal with more T-cell depletion. Clonal studies indicate that BUC after UTUC is also likely luminal, while UTUC after BUC is often basal. CONCLUSIONS: UTUC and BUC share many genomic alterations, but at different frequencies, which recapitulate with their metachronous recurrences. These differences likely contribute to the behavior of these two cancers and imply that they and their metachronous recurrences should be treated as two related yet distinct entities. PATIENT SUMMARY: Urothelial carcinoma of the bladder has distinct genomic features, which are different from distinct genomic features of urothelial carcinoma of the renal pelvis and/or ureter. These features can be used for tailored treatment options specific to tumors of different locations.

Original languageEnglish
Pages (from-to)170-179
Number of pages10
JournalEuropean Urology Oncology
Volume4
Issue number2
DOIs
StatePublished - Apr 1 2021

Keywords

  • Bladder
  • Genetics
  • Renal pelvis
  • Systemic therapy
  • Ureter
  • Urothelial carcinoma

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