Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation. Issue 8 (May 2015)

• Record Type: Journal Article
• Authors: Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H.; Yang, Rui; Killela, Patrick J.; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Liang, Junbo; Wang, Sizhen; Jiao, Yuchen; Yan, Hai; Tao, Hou-Quan
• Is Part Of: European journal of cancer. Volume 51:Issue 8(2015:May)
• Page Start: 969
• Page End: 976
• Publication Date: 2015-05
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.03.010
• Languages: English
• ISSNs: 0959-8049

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab010"> <title id="st175">Abstract</title> <sec> <title id="st125">Background</title> <p id="sp0010">Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (<italic>TERT</italic>) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse <italic>TERT</italic> promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations.</p> </sec> <sec> <title id="st130">Methods</title> <p id="sp0015"> <italic>TERT</italic> promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the <italic>TERT</italic> promoter has not been previously sequenced. Functional studies included <italic>TERT</italic> expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay.</p> </sec> <sec> <title id="st135">Results</title> <p id="sp0020"> <italic>TERT</italic> promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. <italic>TERT</italic> promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. <italic>TERT</italic> promoter mutations highly correlated with upregulated <italic>TERT</italic> mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the <italic>TERT</italic> core promoter.</p> </sec> <sec> <title id="st140">Conclusions</title> <p id="sp0025"> <italic>TERT</italic> promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets.</p> </sec> </abstract>