TERT promoter mutations and gene amplification: Promoting TERT expression in Merkel cell carcinoma
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Hong Xie1,*, Tiantian Liu2,*, Na Wang1, Viveca Björnhagen3, Anders Höög1, Catharina Larsson1, Weng-Onn Lui1 and Dawei Xu4
1 Department of Oncology-Pathology, Cancer Center Karolinska
2 Department of Pathology, Shandong University School of Medicine, Jinan, PR China
3 Department of Reconstructive Plastic Surgery, Karolinska University Hospital Solna, Stockholm, Sweden
4 Department of Medicine-Solna, Division of Hematology and Center for Molecular Medicine. Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden
* These authors contributed equally to this work
Tiantian Liu, email:
Dawei Xu, email:
Keywords: Gene amplification; Merkel cell carcinoma; MCV; Promoter mutations; Telomerase; TERT
Received: July 25, 2014 Accepted: September 15, 2014 Published: September 16, 2014
Telomerase activation through the induction of its catalytic component TERT is essential in carcinogenesis. The regulatory mechanism and clinical significance underlying cancer-specific TERT expression have been extensively investigated in various human malignancies, but little is known about these in Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor. Here we addressed these issues by determining TERT promoter mutations, gene amplification, mRNA expression and association with clinical variables in MCC. TERT mRNA was expressed in 6/6 MCC cell lines and 41 of 43 tumors derived from 35 MCC patients. Telomerase activity was detectable in all 6 cell lines and 11 tumors analyzed. TERT promoter mutations were identified in 1/6 cell lines and 4/35 (11.4%) MCC cases. The mutation exhibited UV signature and occurred in sun-exposed areas. Increased TERT gene copy numbers were observed in 1/6 cell lines and 11/14 (79%) tumors, and highly correlated with its mRNA expression (r = 0.7419, P = 0.0024). Shorter overall survival was significantly associated with higher TERT mRNA levels in MCC patients (P = 0.032). Collectively, TERT expression and telomerase activity is widespread in MCC, and may be attributable to TERT promoter mutations and gene amplification. Higher TERT expression predicts poor patient outcomes.
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