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脑肿瘤细胞系中TERT突变的高发生率。

High incidence of TERT mutation in brain tumor cell lines.

作者信息

Johanns Tanner M, Fu Yujie, Kobayashi Dale K, Mei Yu, Dunn Ian F, Mao Diane D, Kim Albert H, Dunn Gavin P

机构信息

Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Brain Tumor Pathol. 2016 Jul;33(3):222-7. doi: 10.1007/s10014-016-0257-5. Epub 2016 Mar 9.

Abstract

TERT promoter gene mutations are highly recurrent in malignant glioma. However, little information exists regarding their presence in experimental brain tumor models. To better characterize systems in which TERT mutation studies could be appropriately modeled experimentally, the TERT promoter was examined by conventional sequencing in primary brain tumor initiating cells (BTIC), two matched recurrent BTIC lines, a panel of established malignant glioma cell lines, and two meningioma cell lines. Telomerase gene expression was examined by quantitative PCR. We found that all glioblastoma BTIC lines harbored a TERT mutation, which was retained in two patient-matched recurrent BTIC. The TERT C228T or C250T mutation was found in 33/35 (94 %) of established malignant glioma cell lines and both meningioma cell lines examined. Brain tumor cell lines expressed variably high telomerase levels. Thus, a high percentage of glioma cell lines, as well as two meningioma cell lines, harbors TERT mutations. These data characterize tractable, accessible models with which to further explore telomerase biology in these tumor types.

摘要

端粒酶逆转录酶(TERT)启动子基因突变在恶性胶质瘤中高度频发。然而,关于它们在实验性脑肿瘤模型中的存在情况,所知甚少。为了更好地表征可在实验中对TERT突变研究进行适当建模的系统,我们通过常规测序对原发性脑肿瘤起始细胞(BTIC)、两个匹配的复发性BTIC系、一组已建立的恶性胶质瘤细胞系以及两个脑膜瘤细胞系中的TERT启动子进行了检测。通过定量PCR检测端粒酶基因表达。我们发现,所有胶质母细胞瘤BTIC系都存在TERT突变,该突变在两个与患者匹配的复发性BTIC中得以保留。在所检测的35个已建立的恶性胶质瘤细胞系中的33个(94%)以及两个脑膜瘤细胞系中均发现了TERT C228T或C250T突变。脑肿瘤细胞系表达的端粒酶水平高低不一。因此,高比例的胶质瘤细胞系以及两个脑膜瘤细胞系都存在TERT突变。这些数据表征了可用于进一步探索这些肿瘤类型中端粒酶生物学的易于处理、可获取的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b27/5605295/89b9ddb4a0ef/nihms867362f1.jpg

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