TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas
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Ke Gao1,2,*, Gang Li3,*, Yiping Qu1, Maode Wang2, Bo Cui1, Meiju Ji4, Bingyin Shi1, Peng Hou1
1Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, the People's Republic of China
2Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, the People's Republic of China
3Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, the People's Republic of China
4Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, the People's Republic of China
*These authors have contributed equally to this work
Peng Hou, e-mail: firstname.lastname@example.org
Maode Wang, e-mail: email@example.com
Keywords: glioma, TERT promoter mutations, relative telomere length, poor survival, radiotherapy resistance
Received: May 28, 2015 Accepted: October 04, 2015 Published: November 09, 2015
Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P < 0.001), and demonstrated that the RTL was strongly correlated with tumor recurrence. Importantly, TERT promoter mutations or long RTL caused a significantly poorer survival than TERT wild-type or short RTL. Coexisting TERT promoter mutations and long RTL were more commonly associated with poor patient survival than they were individually. Notably, the patients with TERT promoter mutations particularly C228T or long RTL were resistant to radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas.
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