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BACKGROUND  Telomerase reverse transcriptase ( TERT ) promoter mutations that may affect telomerase activity have recently been described in human malignancies. The purpose of this study was to investigate the clinical correlates of  TERT  promoter abnormalities in a large cohort of patients with diverse cancers.    METHODS  This study analyzed  TERT  promoter alterations and clinical characteristics of 423 consecutive patients for whom molecular testing by next‐generation sequencing was performed between August 2014 and July 2015.    RESULTS  Of the 423 patients, 61 (14.4%) had  TERT  promoter mutations, and this placed  TERT  promoter alterations among the most prevalent aberrations after tumor protein 53 ( TP53 ; 39%) and  KRAS  and cyclin‐dependent kinase inhibitor 2A/B ( CDKN2A/B ) alterations (15% each) in this population.  TERT  promoter alterations were more frequent in men ( P  = .031) and were associated with brain cancers ( P  = .001), skin cancers/melanoma ( P  = .001), and a higher number of aberrations ( P  = .0001). A co‐alteration analysis found that  TERT  promoter alterations were significantly correlated with  CDKN2A/B  ( P  = .001) and  BRAF  abnormalities ( P  = .0003). Patients harboring  TERT  promoter alterations or  TP53  or  CDKN2A/B  alterations and those with 4 or more alterations demonstrated shorter survival (hazard ratio for normal  TERT  promoters vs aberrant ones, 0.44;  P  = .017). However, only a higher number of alterations remained significant in the multivariate analysis.    CONCLUSIONS  Overall,  TERT  promoter alterations were among the most prevalent aberrations in this population, with very high rates in brain cancers (48% of patients) and melanomas (56% of patients). These aberrations frequently coexist with a high number of other aberrations, with the latter feature also significantly associated with poorer overall survival. Therapeutic options for targeting tumors with  TERT  promoter mutations are currently limited, although a variety of novel approaches are under development.   Cancer  2018;124:1288‐96.  ©  2017 American Cancer Society .

cancer

Telomerase reverse transcriptase promoter alterations across cancer types as detected by next‐generation sequencing: A clinical and molecular analysis of 423 patients