TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine

Isaac Kinde, Enrico Munari, Sheila F. Faraj, Ralph H. Hruban, Mark P. Schoenberg, Trinity Bivalacqua, Mohamad Allaf, Simeon Springer, Yuxuan Wang, Luis A. Diaz, Kenneth W. Kinzler, Bert Vogelstein, Nickolas Papadopoulos, George J. Netto

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Activating mutations occur in the promoter of the telomerase reverse transcriptase (TERT) gene in 66% of muscle-invasive urothelial carcinomas. To explore their role in bladder cancer development and to assess their utility as urine markers for early detection, we sequenced the TERT promoter in 76 well-characterized papillary and flat noninvasive urothelial carcinomas, including 28 pTa low-grade transitional cell carcinomas (TCC), 31 pTa high-grade TCCs, and 17 pTis carcinoma in situ lesions. We also evaluated the sequence of the TERT promoter in a separate series of 14 early bladder neoplasms and matched follow-up urine samples to determine whether urine TERT status was an indicator of disease recurrence. A high rate of TERT promoter mutation was observed in both papillary and flat lesions, as well as in low- and high-grade noninvasive urothelial neoplasms (mean: 74%). In addition, among patients whose tumors harbored TERT promoter mutations, the same mutations were present in follow-up urines in seven of eight patients that recurred but in none of the six patients that did not recur (P 0.001). TERT promoter mutations occur in both papillary and flat lesions, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and seem to be strongly associated with bladder cancer recurrence. These provocative results suggest that TERT promoter mutations may offer a useful urinary biomarker for both early detection and monitoring of bladder neoplasia.

Original languageEnglish (US)
Pages (from-to)7162-7167
Number of pages6
JournalCancer Research
Volume73
Issue number24
DOIs
StatePublished - Dec 15 2013
Externally publishedYes

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Telomerase
Biomarkers
Urine
Recurrence
Mutation
Neoplasms
Urinary Bladder Neoplasms
Urinary Bladder
Carcinoma
Transitional Cell Carcinoma
Carcinoma in Situ
Muscles
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine. / Kinde, Isaac; Munari, Enrico; Faraj, Sheila F.; Hruban, Ralph H.; Schoenberg, Mark P.; Bivalacqua, Trinity; Allaf, Mohamad; Springer, Simeon; Wang, Yuxuan; Diaz, Luis A.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas; Netto, George J.

In: Cancer Research, Vol. 73, No. 24, 15.12.2013, p. 7162-7167.

Research output: Contribution to journalArticle

Kinde, I, Munari, E, Faraj, SF, Hruban, RH, Schoenberg, MP, Bivalacqua, T, Allaf, M, Springer, S, Wang, Y, Diaz, LA, Kinzler, KW, Vogelstein, B, Papadopoulos, N & Netto, GJ 2013, 'TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine', Cancer Research, vol. 73, no. 24, pp. 7162-7167. https://doi.org/10.1158/0008-5472.CAN-13-2498
Kinde, Isaac ; Munari, Enrico ; Faraj, Sheila F. ; Hruban, Ralph H. ; Schoenberg, Mark P. ; Bivalacqua, Trinity ; Allaf, Mohamad ; Springer, Simeon ; Wang, Yuxuan ; Diaz, Luis A. ; Kinzler, Kenneth W. ; Vogelstein, Bert ; Papadopoulos, Nickolas ; Netto, George J. / TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine. In: Cancer Research. 2013 ; Vol. 73, No. 24. pp. 7162-7167.
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AU - Hruban, Ralph H.

AU - Schoenberg, Mark P.

AU - Bivalacqua, Trinity

AU - Allaf, Mohamad

AU - Springer, Simeon

AU - Wang, Yuxuan

AU - Diaz, Luis A.

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Papadopoulos, Nickolas

AU - Netto, George J.

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