Guo Yuchen, Chen Yi, Zhang Lianghui, Ma Ling, Jiang Keyu, Yao Gang, Zhu Lingjun
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Plastic and Burns Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
J Oncol. 2022 Jul 19;2022:6300329. doi: 10.1155/2022/6300329. eCollection 2022.
Malignant melanoma is an extremely malignant tumor with a high mortality rate and an increasing incidence with a high mutation load. The frequency of mutations in the TERT promoter exceeds the frequency of any known noncoding mutations in melanoma. A growing number of recent studies suggest that the most common mutations in the TERT promoter (ATG start site -124C>T and -146C>T) are associated with increased TERT mRNA expression, telomerase activity, telomere length, and poor prognosis. Recently, it has been shown that TERT promoter mutations are more correlated with the occurrence, development, invasion, and metastasis of melanoma, as well as emerging approaches such as the therapeutic potential of chemical inhibition of TERT promoter mutations, direct telomerase inhibitors, combined targeted therapy, and immunotherapies. In this review, we describe the latest advances in the role of TERT promoter mutations and telomerase in promoting the occurrence, development, and poor prognosis of melanoma and discuss the clinical significance of the TERT promoter and telomerase in the treatment of melanoma.
恶性黑色素瘤是一种极具侵袭性的肿瘤,死亡率高,发病率呈上升趋势,且具有高突变负荷。端粒酶逆转录酶(TERT)启动子的突变频率超过了黑色素瘤中任何已知的非编码突变频率。最近越来越多的研究表明,TERT启动子中最常见的突变(ATG起始位点-124C>T和-146C>T)与TERT信使核糖核酸(mRNA)表达增加、端粒酶活性、端粒长度以及不良预后相关。最近有研究表明,TERT启动子突变与黑色素瘤的发生、发展、侵袭和转移更为相关,同时也与一些新兴的治疗方法相关,如化学抑制TERT启动子突变的治疗潜力、直接端粒酶抑制剂、联合靶向治疗和免疫疗法。在本综述中,我们描述了TERT启动子突变和端粒酶在促进黑色素瘤发生、发展及不良预后方面作用的最新进展,并讨论了TERT启动子和端粒酶在黑色素瘤治疗中的临床意义。