Article
TERT and its binding protein – overexpression of GABPA/B in high-grade gliomas
TERT und seine Bindungsproteine – Überexpression von GABPA/B in malignen Gliomen
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Authors
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Efthymios Papazacharias
- Klinikum rechts der Isar München, Neurochirurgie, München, Deutschland
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Saskia Kuhl
- Universitätsklinikum Köln, Klinik für Neurochirurgie, Köln, Deutschland
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Roland H. Goldbrunner
- Universitätsklinikum Köln, Klinik für Neurochirurgie, Köln, Deutschland
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Marco Timmer
- Universitätsklinikum Köln, Klinik für Neurochirurgie, Köln, Deutschland
| Published: | June 26, 2020 |
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Outline
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Objective: Enhanced expression of TERT in gliomas is a result of two hotspot mutations, C228T and C250T, at the promoter region. The GABP of the ETS family selectively binds at these positions respectively causing an activation of the promoter and overexpression of TERT. GABP is a multimeric protein consisting of GABPA and GABPB with its isoforms GABPB1, GABPB1-L, GABPB1-S, GABPB2. In this study, we investigated the expression of TERT and GABPA/B isoforms in the glioma grades.
Methods: Glioma tumor samples were stored in frozen liquid nitrogen at -80 ̊C. We performed quantitative real time-PCR for TERT and GABPA/B isoforms in controls, grade II, III gliomas and primary, secondary glioblastomas with and without chemotherapy with use of SYBR green and SDHA as the housekeeping gene. The statistic was analyzed with Kruskal-Wallis, Mann-Whitney-U-test and correlation.
Results: TERT is mainly expressed in primary glioblastomas. All GA-binding proteins progress throw the glioma grades and in secondary glioblastomas they have the highest expression levels (A: mean= 0.221, 95% CI= 0.09-0.35, B1: 0.66, 0.52-0.8, B1-L: 0.705, 0.48-0.92, B1-S: 0.836, 0.46-1.2). In secondary glioblastomas after chemotherapy, B1 (0.308 ± 0.198; p=0.001) and B1-L (0.464 ± 0.495; p=0.035) are lower expressed than without treatment. In high grades TERT, A, B1, B1-L, B1-S are statistically significant overexpressed compared to low grades. Between primary and secondary glioblastomas with and without chemotherapy, TERT is overexpressed in the former (0.118, 0.05-0.17; p< 0.0001) while B1 is increased in the secondary glioblastomas of the same treatment status (0.484, 0.36-0.6; p= 0.043). In primary glioblastomas B1-S tends to positive correlate with TERT.
Conclusion: TERT is mostly expressed in primary glioblastomas. GABPA/B levels are rising with the malignancy of gliomas with the most expression in the secondary glioblastomas. Chemotherapy treatment decreases the expression of B1 and B1-L in secondary glioblastomas and in high grades TERT, A, B1, B1-L, B1-S are overexpressed. In primary glioblastomas B1-S has a trend to increase with TERT overexpression. The association between TERT and GABPA/B isoforms in gliomas could be an aim for a targeted therapy.
