Elevated TERT Expression in TERT-Wildtype Adult Diffuse Gliomas: Histological Evaluation with a Novel TERT-Specific Antibody

TERT 野生型成人弥漫性胶质瘤中 TERT 表达升高:使用新型 TERT 特异性抗体进行组织学评估

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作者:Kenta Masui, Takashi Komori, Yukinari Kato, Kenkichi Masutomi, Koichi Ichimura, Satoshi Ogasawara, Mika K Kaneko, Hiroharu Oki, Hiroyoshi Suzuki, Masayuki Nitta, Takashi Maruyama, Yoshihiro Muragaki, Takakazu Kawamata, Tatsuo Sawada, Noriyuki Shibata

Abstract

Telomerase reverse transcriptase (TERT) is important for the biology of diffuse gliomas. TERT promoter mutations are selectively observed among 1p/19q-codeleted oligodendrogliomas and isocitrate dehydrogenase gene- (IDH-) wildtype glioblastoma (GBM). However, TERT transcripts range widely in various cancers including gliomas, and TERT protein expression has been rarely investigated thus far. It would be thus critical to examine the expression level of TERT in tumors in addition to its mutational status, and sensitive and specific methods are urgently needed to examine TERT protein expression for the assessment of TERT biology in gliomas. Using our newly developed TERT-specific monoclonal antibody (TMab-6) applicable to human tissue, we found an unexpected increase in TERT expression in TERT-wildtype as well as TERT-mutated gliomas and in tumor vasculature. This is the first extensive analysis on the expression of TERT immunoreactivity in human glioma tissue, suggesting that TERT protein expression may be regulated by several mechanisms in addition to its promoter mutation.

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