Oncotarget

Clinical Research Papers:

TERT promoter mutations and telomere length in adult malignant gliomas and recurrences

Barbara Heidenreich _, Sivaramakrishna P. Rachakonda, Ismail Hosen, Florian Volz, Kari Hemminki, Astrid Weyerbrock and Rajiv Kumar

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Oncotarget. 2015; 6:10617-10633. https://doi.org/10.18632/oncotarget.3329

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Abstract

Barbara Heidenreich1, P. Sivaramakrishna Rachakonda1, Ismail Hosen1, Florian Volz2, Kari Hemminki1,3, Astrid Weyerbrock2, Rajiv Kumar1

1Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany

2Department of Neurosurgery, University Medical Center Freiburg, Freiburg 79106, Germany

3Center for Primary Health Care Research, Lund University, Malmö, Lund 22100, Sweden

Correspondence to:

Barbara Heidenreich, e-mail: b.heidenreich@dkfz.de

Rajiv Kumar, e-mail: r.kumar@dkfz.de

Keywords: Gliomas, TERT promoter, IDH, telomere length, TERT expression

Received: January 07, 2015     Accepted: February 09, 2015     Published: March 12, 2015

ABSTRACT

In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5–250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03–0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with increased survival (P = 0.0004). TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 – 55.9). While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome.


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