TERT PROMOTER MUTATION

第三启动子突变是激活的，通常在第三启动子区域的两个热点处发现，在翻译起始位点上游出现124和146碱基对（hg19）。这些热点被称为C228T和C250T，在许多癌症类型中都有观察到，在胶质母细胞瘤（83%）、黑色素瘤（71%）、膀胱癌（66%）和肝细胞癌（47%）中的发病率特别高。这两个突变通常是杂合子，相互排斥，导致与ETS结合域的相似性增加，并可能作为与ETS转录因子的结合位点。这些突变被认为是肿瘤发生的早期事件，有助于细胞的永生。在髓母细胞瘤、甲状腺癌、泌尿生殖道癌、黑色素瘤和喉部肿瘤中观察到这些突变患者的总生存率下降。这些突变的存在也被证明可以预测肝癌和脑膜瘤的恶性/癌前结节。
TERT promoter mutations are activating and commonly found at two hotspots within the TERT promoter region which occur 124 and 146 base pairs (hg19) upstream of the translation start site. These hotspots, termed C228T and C250T are observed in many cancer types and have a particularly high prevalence in glioblastoma (83%), melanoma (71%), bladder cancer (66%) and hepatocelluar carcinoma (HCC) (47%). The two mutations are usually heterozygous and mutually exclusive and result in an increased similarity to an ETS binding domain and may act as a binding site to an ETS transcription factor. These mutations are thought to be early events in tumorgenesis and aid in cellular immortality. Decreased overall survival in patients with these mutations have been observed in medulloblastoma, thyroid cancer, urogenital cancer, melanoma, and laryngeal tumors. The presence of these mutations has also been shown to be predictive of malignant/premalignant nodules in HCC and meningiomas.