title: TERT promoter mutations and telomere length in adult malignant gliomas and recurrences.
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.
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany.
authors: Barbara
authors: B
authors: Heidenreich
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany.
authors: P Sivaramakrishna
authors: PS
authors: Rachakonda
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany.
authors: Ismail
authors: I
authors: Hosen
authors: Department of Neurosurgery, University Medical Center Freiburg, Freiburg 79106, Germany.
authors: Florian
authors: F
authors: Volz
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany.|Center for Primary Health Care Research, Lund University, Malmö, Lund 22100, Sweden.
authors: Kari
authors: K
authors: Hemminki
authors: Department of Neurosurgery, University Medical Center Freiburg, Freiburg 79106, Germany.
authors: Astrid
authors: A
authors: Weyerbrock
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany.
authors: Rajiv
authors: R
authors: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics; D055815:Young Adult
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: IDH; TERT expression; TERT promoter; gliomas; telomere length