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Oncotarget. 2014;5(10):3399-407.

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

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제1저자 박철기 · 교신저자 박철기/이세훈

소속 (2)
  1. Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea;Department of Biomedical Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
  2. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.

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.

Figures

Figure 1
Figure 1 A. Distribution of hTERT promoter genetic events and other molecular characteristics in 48 glioblastoma patients. The cases are ordered by priority of age. B. Mosaic plot for somatic mutation (C228T or C250T) and common polymorphism (T349C) in the hTERT promoter region, MGMT promoter methylation and EGFR amplification. The colored cells show significant magnitude of the Pearson residuals (≥ 2.0) obtained from an independence model.
Figure 2
Figure 2 Difference in age distribution according to the hTERT existence of the promoter somatic mutation (C228T or C250T) in glioblastoma patients Data represent mean ± 95% confidential interval. *, p ≤ 0.05.
Figure 3
Figure 3 hTERT expression in glioblastomas A. Quantitative real time-PCR (Q-PCR) result shows significant hTERT overexpression in C228T or C250T mutation samples. B. No differences in hTERT expression between C228T and C250T mutation samples were observed by Q-PCR. C. Visualization of reverse transcriptase PCR (RT-PCR) results by groups of hTERT promoter genetic events. D. Q-PCR results by groups of hTERT promoter genetic events. Data represent mean ± 95% confidential interval. *, p ≤ 0.05.
Figure 4
Figure 4 Kaplan–Meier survival plot and the log rank test results for overall survival (A-C) and progression-free survival (D-F) in patients with and without the hTERT promoter mutation, the common polymorphism, and their combination

그림 출처: PubMed Central 공개 논문 (PMC4102818)

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Oncotarget · eISSN 1949-2553
MeSH
Adult · Brain Neoplasms / enzymology / genetics / mortality · Female · Genotype · Glioblastoma / enzymology / genetics / mortality · Humans · In Situ Hybridization, Fluorescence · Kaplan-Meier Estimate · Male · Middle Aged · Mutation* · Oligonucleotide Array Sequence Analysis · Polymorphism, Single Nucleotide* · Promoter Regions, Genetic / genetics · Real-Time Polymerase Chain Reaction · Reverse Transcriptase Polymerase Chain Reaction · Telomerase / biosynthesis / genetics
Substances
Telomerase
참고문헌
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