Department of Neurological Surgery, Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143-0520, USA.
J Neurooncol. 2012 Dec;110(3):305-13. doi: 10.1007/s11060-012-0973-6. Epub 2012 Sep 17.
Diffuse intrinsic pontine gliomas arise almost exclusively in children, and despite advances in treatment, the majority of patients die within 2 years after initial diagnosis. Because of their infiltrative nature and anatomic location in an eloquent area of the brain, most pontine gliomas are treated without a surgical biopsy. The corresponding lack of tissue samples has resulted in a limited understanding of the underlying genetic and molecular biologic abnormalities associated with pontine gliomas, and is a substantial obstacle for the preclinical testing of targeted therapeutic agents for these tumors. We have established a human glioma cell line that originated from surgical biopsy performed on a patient with a pontine glioma. To insure sustainable in vitro propagation, tumor cells were modified with hTERT (human telomerase ribonucleoprotein reverse transcriptase), and with a luciferase reporter to enable non-invasive bioluminescence imaging. The hTERT modified cells are tumorigenic in athymic rodents, and produce brainstem tumors that recapitulate the infiltrative growth of brainstem gliomas in patients.
弥漫性内在脑桥神经胶质瘤几乎仅发生于儿童，尽管治疗手段已有进展，但大多数患者在初始诊断后 2 年内死亡。由于其浸润性和位于大脑功能区的解剖位置，大多数脑桥神经胶质瘤在不进行手术活检的情况下进行治疗。相应的缺乏组织样本导致对与脑桥神经胶质瘤相关的潜在遗传和分子生物学异常的了解有限，这是对这些肿瘤的靶向治疗药物进行临床前测试的一个重大障碍。我们建立了一个源自脑桥神经胶质瘤患者手术活检的人神经胶质瘤细胞系。为了确保可持续的体外繁殖，肿瘤细胞被 hTERT（人端粒酶核糖核蛋白逆转录酶）修饰，并带有荧光素酶报告基因，以实现非侵入性生物发光成像。经过 hTERT 修饰的细胞在无胸腺啮齿动物中具有致瘤性，并产生脑干部位肿瘤，这些肿瘤再现了患者脑干部位神经胶质瘤的浸润性生长。
