The clonal relation of primary upper urinary tract urothelial carcinoma and paired urothelial carcinoma of the bladder

Int J Cancer. 2021 Feb 15;148(4):981-987. doi: 10.1002/ijc.33327. Epub 2020 Oct 13.

Abstract

The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities.

Keywords: bladder carcinoma; clonality; upper urinary tract carcinoma; urothelial carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / surgery
  • Clone Cells / metabolism
  • Clone Cells / pathology
  • Female
  • Gene Expression Profiling / methods
  • Genomics / methods
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery
  • Male
  • Middle Aged
  • Nephroureterectomy / methods*
  • Polymorphism, Single Nucleotide
  • Ureteral Neoplasms / genetics*
  • Ureteral Neoplasms / pathology
  • Ureteral Neoplasms / surgery
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery
  • Urinary Tract / metabolism*
  • Urinary Tract / pathology
  • Urinary Tract / surgery