TERT promoter mutations rather than methylation are the main mechanism for TERT upregulation in adult gliomas
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Telomere lengthening (TL) is mandatory for infinite proliferation of many cancer cells. This is generally achieved either by telomerase activation or in some cases by telomerase-independent alternative lengthening of telomeres (ALT) . Recently, recurrent mutations at two hotspots termed C228T and C250T in the promoter region of TERT, a catalytic subunit of telomerase, have been reported in various types of cancers [1, 6, 7, 9, 12]. These mutations result in upregulation of TERT expression [1, 7], which is required for telomerase activation . TERT promoter mutations are particularly common in adult gliomas [1, 9]. It is also known that a subset of astrocytomas harbors mutations of ATRX, which could lead to ALT .
We have previously shown that glioblastomas with TERT mutation had TERT mRNA upregulation . We have also observed TERT upregulation in some tumors without mutations in the hotspots. A small subset of tumors had neither TERT nor ATRX mutations . Recently, it has...
KeywordsMethylation Status Methylation Level Promoter Mutation Oligodendroglial Tumor TERT Promoter Mutation
This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan [No. 24659650 (H.A.)], and by the National Cancer Center Research and Development Fund [23-A-50 (K.I.)]. The authors thank Dr Sylvia Kocialkowski for critical reading of the manuscript.
- 1.Arita H, Narita Y, Fukushima S, Tateishi K, Matsushita Y, Yoshida A, Miyakita Y, Ohno M, Collins VP, Kawahara N, Shibui S, Ichimura K (2013) Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol 126:267–276PubMedCrossRefGoogle Scholar
- 8.Ichimura K, Nishikawa R, Matsutani M (2012) Molecular markers in pediatric neuro-oncology. Neuro Oncol 14 Suppl 4: iv90-99Google Scholar