TERT promoter mutations and telomerase reactivation in urothelial cancer
Menée sur 23 lignées cellulaires et deux cohortes de patients atteints d'un cancer urothélial, cette étude suggère qu'une mesure d'activité de la télomérase est un meilleur marqueur de l'agressivité des tumeurs que la détection de mutations de la séquence promotrice du gène TERT
Reactivation of telomerase, the chromosome end-replicating enzyme, drives human cell immortality and cancer. Point mutations in the telomerase reverse transcriptase (TERT) gene promoter occur at high frequency in multiple cancers, including urothelial cancer (UC), but their impact on telomerase function has been unclear. In a study of 23 human UC cell lines, we show that these promoter mutations correlate with higher levels of TERT mRNA, TERT protein, telomerase enzymatic activity and telomere length. While previous studies found no relationship between TERT promoter mutations and UC patient outcome, we find that elevated TERT mRNA expression strongly correlates with reduced disease-specific survival (DSS) in two independent UC patient cohorts (n = 35; n = 87). These results suggest that high telomerase activity may be a better marker of aggressive UC tumors than TERT promoter mutations alone.
Science , résumé, 2015