癌症。膀胱癌中 TERT 启动子突变与端粒酶激活。
Cancer. TERT promoter mutations and telomerase reactivation in urothelial cancer.
机构信息
Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, CO 80309, USA. Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, CO 80309, USA. Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
出版信息
Science. 2015 Feb 27;347(6225):1006-10. doi: 10.1126/science.1260200. Epub 2015 Feb 5.
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 effect 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 messenger RNA (mRNA), TERT protein, telomerase enzymatic activity, and telomere length. Although previous studies found no relation between TERT promoter mutations and UC patient outcome, we find that elevated TERT mRNA expression strongly correlates with reduced disease-specific survival 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.
端粒酶的重新激活，即染色体末端复制酶，推动了人类细胞的永生和癌症的发生。端粒酶逆转录酶（TERT）基因启动子中的点突变在多种癌症中高频发生，包括膀胱癌（UC），但其对端粒酶功能的影响尚不清楚。在对 23 个人类 UC 细胞系的研究中，我们表明这些启动子突变与更高水平的 TERT 信使 RNA（mRNA）、TERT 蛋白、端粒酶酶活性和端粒长度相关。尽管先前的研究发现 TERT 启动子突变与 UC 患者的预后无关，但我们发现，在两个独立的 UC 患者队列（n=35；n=87）中，高 TERT mRNA 表达与疾病特异性生存率降低显著相关。这些结果表明，高端粒酶活性可能是比 TERT 启动子突变更能预测侵袭性 UC 肿瘤的标志物。
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