Detection of TERT promoter mutations in primary adenocarcinoma of the urinary bladder

Hum Pathol. 2016 Jul;53:8-13. doi: 10.1016/j.humpath.2016.02.009. Epub 2016 Mar 10.

Abstract

TERT promoter mutations (TERT-mut) have been detected in 60% to 80% of urothelial carcinomas. A molecular urine-based screening assay for the detection of TERT-mut is currently being pursued by our group and others. A small but significant number of bladder carcinomas are adenocarcinoma. The current study assesses the incidence of TERT-mut in primary adenocarcinomas of urinary bladder. A retrospective search of our institutional pathology records identified 23 cystectomy specimens with a diagnosis of adenocarcinoma (2000-2014). All slides were reviewed by a senior urologic pathologist to confirm tumor type and select a representative formalin-fixed, paraffin-embedded block for mutational analysis. Adequate material for DNA testing was available in 14 cases (7 enteric type and 7 not otherwise specified). TERT-mut sequencing analysis was performed using previously described SafeSeq technique. Overall, 28.5% of primary adenocarcinoma harbored TERT-mut. Interestingly, 57% of nonenteric adenocarcinomas were mutation positive, whereas none of the enteric-type tumors harbored mutations. Similar to urothelial carcinoma, we found a relatively higher rate of TERT-mut among nonenteric-type adenocarcinomas further supporting the potential utility of TERT-mut urine-based screening assay for bladder cancer.

Keywords: Adenocarcinoma; Bladder carcinoma; Mutation; TERT; Telomerase; Telomerase reverse transcriptase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Baltimore
  • Biomarkers, Tumor / genetics*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Promoter Regions, Genetic*
  • Retrospective Studies
  • Telomerase / genetics*
  • Urinary Bladder Neoplasms / enzymology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • TERT protein, human
  • Telomerase