Molecular classification and diagnostics of upper urinary tract urothelial carcinoma

Cancer Cell. 2021 Jun 14;39(6):793-809.e8. doi: 10.1016/j.ccell.2021.05.008.


Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification. According to the mutational status of TP53, MDM2, RAS, and FGFR3, UTUC is classified into five subtypes having discrete profiles of gene expression, tumor location/histology, and clinical outcome, which is largely recapitulated in an independent UTUC cohort. Sequencing of urine sediment-derived DNA has a high diagnostic value for UTUC with 82.2% sensitivity and 100% specificity. These results provide a solid basis for better diagnosis and management of UTUC.

Keywords: FGFR3; RAS; TP53; hypermutation; integrated molecular study; molecular classification; molecular diagnostic; transcriptome; upper urinary tract urothelial carcinoma; urothelial carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / urine*
  • Carcinoma, Transitional Cell / diagnosis*
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / mortality
  • DNA Methylation
  • Female
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Ureteral Neoplasms / diagnosis*
  • Ureteral Neoplasms / genetics*
  • Ureteral Neoplasms / mortality
  • ras Proteins / genetics


  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3
  • ras Proteins