Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling

Nat Commun. 2019 Jul 5;10(1):2977. doi: 10.1038/s41467-019-10873-y.


Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / immunology
  • Carcinoma, Transitional Cell / pathology*
  • DNA Mutational Analysis
  • Down-Regulation
  • Exome Sequencing
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology*
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mutation
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism*
  • Sequence Analysis, RNA
  • Signal Transduction / genetics
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment / immunology
  • Ureteral Neoplasms / genetics
  • Ureteral Neoplasms / immunology
  • Ureteral Neoplasms / pathology*
  • Urothelium / pathology


  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3