Oncotarget

Research Papers:

Expression level of hTERT is regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma

Chul-Kee Park _, Se-Hoon Lee, Ji Young Kim, Ja Eun Kim, Tae Min Kim, Soon-Tae Lee, Seung Hong Choi, Sung-Hye Park and Il Han Kim

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2014; 5:3399-3407. https://doi.org/10.18632/oncotarget.1975

Metrics: PDF 1997 views  |   HTML 2327 views  |   ?  


Abstract

Chul-Kee Park1,7, Se-Hoon Lee2,8, Ji Young Kim1,7, Ja Eun Kim1,7, Tae Min Kim2,8, Soon-Tae Lee3,7, Seung Hong Choi4,7, Sung-Hye Park5,9, Il Han Kim6,8

1 Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea

2 Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea

3 Department of Neurology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea

4 Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea

5 Department of Pathology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea

6 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea

7 Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea

8 Cancer Research Institute, Seoul National University College of Medicine,  Seoul, Korea

9 Neuroscience Institute, Seoul National University College of Medicine,  Seoul, Korea

Correspondence:

Chul-Kee Park , email:

Se-Hoon Lee, email:

Keywords: Glioblastoma, hTERT, promoter mutation, hTERT expression, single nucleotide polymorphism, rs2853669

Received: May 8, 2014 Accepted: May 12, 2014 Published: May 14, 2014

Abstract

We investigated the role of somatic mutations and a common single nucleotide polymorphism (SNP) in the hTERT promoter region on hTERT expression and clinical outcomes. The hTERT promoter region was sequenced from 48 glioblastomas. hTERT expression was analyzed by quantitative real time-PCR. The association between hTERT promoter genetic changes and other genomic events and clinical variables common in gliomas were examined. C228T and C250T somatic mutations were found in 60.4% of glioblastomas, and a common SNP (T349C) was found in 66.6%. Somatic mutations and the SNP likely have opposing effects on hTERT expression. hTERT expression was significantly higher in the C228T or C250T mutated tumors. Tumors with the T349C genotype showed lower hTERT expression when C228T or C250T mutations were present. However, no significant survival differences were observed among the groups with or without hTERT promoter mutations and SNP. There was a significant association between genetic changes in the hTERT promoter and patient age as well as MGMT promoter methylation and EGFR amplification. hTERT expression is modulated by somatic mutations in the hTERT promoter as well as a common polymorphism. However, hTERT related genomic changes have limited value as an independent prognostic factor for clinical outcomes in glioblastomas.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 1975