TERT promoter mutations and telomere length in adult malignant gliomas and recurrences.
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.
['Heidenreich|Barbara|B|', 'Rachakonda|P Sivaramakrishna|PS|', 'Hosen|Ismail|I|', 'Volz|Florian|F|', 'Hemminki|Kari|K|', 'Weyerbrock|Astrid|A|', 'Kumar|Rajiv|R|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D001932:Brain Neoplasms D002648:Child D018572:Disease-Free Survival D005260:Female D005910:Glioma D006801:Humans D008297:Male D008875:Middle Aged D009154:Mutation D009364:Neoplasm Recurrence, Local D011379:Prognosis D011401:Promoter Regions, Genetic D019098:Telomerase D016615:Telomere D055815:Young Adult
TERT promoter telomere length gliomas IDH TERT expression