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

Heidenreich, Barbara; Rachakonda, P Sivaramakrishna; Hosen, Ismail; Volz, Florian; Hemminki, Kari LU ; Weyerbrock, Astrid and Kumar, Rajiv (2015) In Oncotarget 6(12). p.10617-10633
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Oncotarget
volume
6
issue
12
pages
10617 - 10633
publisher
Impact Journals, LLC
external identifiers
  • pmid:25797251
  • wos:000358874600074
  • scopus:84929600818
ISSN
1949-2553
language
English
LU publication?
yes
id
98b58181-8d57-4061-a8fc-cec68fe51d70 (old id 5257878)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25797251?dopt=Abstract
date added to LUP
2015-04-05 13:52:58
date last changed
2017-10-22 04:09:30
@article{98b58181-8d57-4061-a8fc-cec68fe51d70,
  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 &lt; 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.},
  author       = {Heidenreich, Barbara and Rachakonda, P Sivaramakrishna and Hosen, Ismail and Volz, Florian and Hemminki, Kari and Weyerbrock, Astrid and Kumar, Rajiv},
  issn         = {1949-2553},
  language     = {eng},
  number       = {12},
  pages        = {10617--10633},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {TERT promoter mutations and telomere length in adult malignant gliomas and recurrences.},
  volume       = {6},
  year         = {2015},
}