TERT Promoter Mutations Occur Early in Urothelial Neoplasia and are Biomarkers of Early Disease and Disease Recurrence in Urine
Menée sur deux cohortes de patients atteints d'un cancer de la vessie de stade précoce, cette étude suggère que l'identification de mutations du promoteur du gène TERT dans les urines pourrait servir de biomarqueur pour la détection précoce de la maladie et le suivi thérapeutique
We recently reported activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in 66% of muscle-invasive urothelial carcinomas. To further explore the role of TERT mutations 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 (pTa LG) transitional cell carcinomas (TCC), 31 pTa high-grade (pTa HG) TCCs, and 17 pTis carcinoma in situ (CIS) 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 if 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%). Additionally, 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 6 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 appear to be strongly associated with bladder cancer recurrence. These promising preliminary results suggest that TERT promoter mutations may prove to be a useful urinary biomarker for both the early detection and monitoring of bladder neoplasia.
Cancer Research , résumé, 2013