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TERT 基因在 TERT 野生型成人弥漫性胶质瘤中的高表达:新型 TERT 特异性抗体的组织学评估。

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

机构信息

Department of Pathology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.

Department of Neuropathology, Tokyo Metropolitan Neurological Hospital, Tokyo 183-0042, Japan.

出版信息

Biomed Res Int. 2018 Mar 5;2018:7945845. doi: 10.1155/2018/7945845. eCollection 2018.

DOI:10.1155/2018/7945845
PMID:29693015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5859900/
Abstract

Telomerase reverse transcriptase (TERT) is important for the biology of diffuse gliomas. promoter mutations are selectively observed among 1p/19q-codeleted oligodendrogliomas and isocitrate dehydrogenase gene- 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 -wildtype as well as -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.

摘要

端粒酶逆转录酶(TERT)对于弥漫性神经胶质瘤的生物学特性非常重要。1p/19q 缺失型少突胶质细胞瘤和异柠檬酸脱氢酶基因野生型胶质母细胞瘤(GBM)中选择性观察到启动子突变。然而,TERT 转录本在包括神经胶质瘤在内的各种癌症中广泛存在,到目前为止,TERT 蛋白的表达很少被研究。因此,除了突变状态外,检查肿瘤中 TERT 的表达水平至关重要,并且迫切需要敏感和特异的方法来检测 TERT 蛋白表达,以评估 TERT 在神经胶质瘤中的生物学特性。使用我们新开发的适用于人类组织的 TERT 特异性单克隆抗体(TMab-6),我们发现野生型和突变型神经胶质瘤以及肿瘤血管中的 TERT 表达意外增加。这是首次对人类神经胶质瘤组织中 TERT 免疫反应性表达的广泛分析,提示 TERT 蛋白表达可能除了启动子突变之外,还受到几种机制的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/7664f5fbe1b4/BMRI2018-7945845.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/432a9b1b62f6/BMRI2018-7945845.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/f58df2fbcb58/BMRI2018-7945845.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/74ba3c742b0a/BMRI2018-7945845.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/7664f5fbe1b4/BMRI2018-7945845.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/432a9b1b62f6/BMRI2018-7945845.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/f58df2fbcb58/BMRI2018-7945845.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/74ba3c742b0a/BMRI2018-7945845.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2300/5859900/7664f5fbe1b4/BMRI2018-7945845.004.jpg

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本文引用的文献

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Brain Tumor Pathol. 2017 Oct;34(4):139-140. doi: 10.1007/s10014-017-0299-3.
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Establishment of Anti-Human ATRX Monoclonal Antibody AMab-6.
一种用于识别低级别胶质瘤中启动子突变高危肿瘤的定性特征。
Front Mol Biosci. 2022 Apr 14;9:806727. doi: 10.3389/fmolb.2022.806727. eCollection 2022.
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Detection of Promoter Mutations as a Prognostic Biomarker in Gliomas: Methodology, Prospects, and Advances.检测启动子突变作为胶质瘤的预后生物标志物:方法、前景与进展
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