Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Moores Cancer Center at UC San Diego Health, La Jolla, California.
Department of Translational Neuro-Oncology and Neurotherapeutics, John Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center, Santa Monica, California.
Cancer. 2018 Mar 15;124(6):1288-1296. doi: 10.1002/cncr.31175. Epub 2017 Dec 6.
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.
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.
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.
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.
端粒酶逆转录酶（TERT）启动子突变可能影响端粒酶活性，最近在人类恶性肿瘤中已有描述。本研究的目的是在一个多样化癌症患者的大队列中研究 TERT 启动子异常的临床相关性。
本研究分析了 423 例连续患者的 TERT 启动子改变和临床特征，这些患者在 2014 年 8 月至 2015 年 7 月期间进行了下一代测序的分子检测。
在这 423 名患者中，有 61 名（14.4%）有 TERT 启动子突变，在该人群中，TERT 启动子改变是继肿瘤蛋白 53（TP53；39%）和 KRAS 以及细胞周期蛋白依赖性激酶抑制剂 2A/B（CDKN2A/B；15%）之后最常见的异常之一。TERT 启动子改变在男性中更为常见（P =.031），并且与脑癌（P =.001）、皮肤癌/黑色素瘤（P =.001）和更高数量的异常（P =.0001）相关。共同改变分析发现，TERT 启动子改变与 CDKN2A/B（P =.001）和 BRAF 异常（P =.0003）显著相关。携带 TERT 启动子改变或 TP53 或 CDKN2A/B 改变以及有 4 个或更多改变的患者生存时间更短（正常 TERT 启动子与异常 TERT 启动子的风险比为 0.44；P =.017）。然而，只有更多的改变在多变量分析中仍然显著。
总的来说，TERT 启动子改变是该人群中最常见的异常之一，脑癌（48%的患者）和黑色素瘤（56%的患者）的发生率非常高。这些异常经常与大量其他异常共存，后者也与总体生存较差显著相关。目前针对 TERT 启动子突变肿瘤的治疗选择有限，尽管有许多新的方法正在开发中。癌症 2018;124:1288-96。 © 2017 美国癌症协会。
