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Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss
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Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss
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Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss
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Journal Article
Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss
2013
Overview
Telomere lengthening is one of the key events in most cancers, and depends largely on telomerase activation. Telomerase activation is a well-known phenomenon in gliomas; however, its mechanism remains obscure. In this study, we investigated the presence of mutations in the promoter of the telomerase reverse transcriptase (
TERT
) gene in a series of 546 gliomas. We found a high incidence of mutually exclusive mutations located at two hot spots, C228T and C250T, in all subtypes of gliomas (55 %). The frequency of mutation was particularly high among primary glioblastomas (70 %) and pure oligodendroglial tumors (74 %), while relatively low in diffuse astrocytomas and anaplastic astrocytomas (19 and 25 %, respectively). The expression level of
TERT
in tumors carrying those mutations was on average 6.1 times higher than that of wild-type tumors, indicating that the mutated promoter leads to upregulation of
TERT
.
TERT
promoter mutations were observed in almost all tumors harboring concurrent total 1p19q loss and
IDH1/2
mutations (98 %). Otherwise
TERT
promoter mutations were mostly observed among
IDH
wild-type tumors. Most
EGFR
amplifications (92 %) were also associated with
TERT
promoter mutations. Our data indicate that mutation of the
TERT
promoter is one of the major mechanisms of telomerase activation in gliomas. The unique pattern of
TERT
promoter mutations in relation to other genetic alterations suggests that they play distinct roles in the pathogenesis of oligodendroglial and astrocytic tumors. Our results shed a new light on the role of telomerase activation in the development of adult gliomas.
Publisher
Springer Berlin Heidelberg,Springer,Springer Nature B.V
