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低级别胶质瘤的分子研究进展、治疗和预后

Update on molecular findings, management and outcome in low-grade gliomas.

机构信息

University of Virginia Health System, Department of Pathology, Division of Neuropathology, Charlottesville, VA 22908-0214, USA.

出版信息

Nat Rev Neurol. 2010 Dec;6(12):695-701. doi: 10.1038/nrneurol.2010.159. Epub 2010 Nov 2.

Abstract

Low-grade infiltrating gliomas in adults include diffuse astrocytoma, oligoastrocytoma and oligodendroglioma. The current gold standard diagnosis of these tumors relies on histological classification; however, emerging molecular abnormalities discovered in these tumors are playing an increasingly prominent part in the process of tumor diagnosis and, consequently, patient management. The frequency and clinical importance of tumor protein p53 (TP53) abnormalities, deletions involving chromosomes 1p and 19q, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, abnormalities in the PTEN tumor suppressor gene and the BRAF oncogene, and isocitrate dehydrogenase (IDH) mutations have become better defined. Molecular markers have not, historically, had an important role in determining the course of treatment for patients with low-grade gliomas, but ongoing phase III clinical trials incorporate 1p deletion or 1p19q codeletion status-and future trials plan to incorporate MGMT promoter methylation status-as stratification factors. Future trials will need to incorporate IDH mutational status in addition to these factors. Ultimately, molecular marker assessment will, hopefully, improve the accuracy of tumor diagnosis and enhance the effectiveness of treatment to achieve improved patient outcomes.

摘要

成人低级别浸润性神经胶质瘤包括弥漫性星形细胞瘤、少突星形细胞瘤和少突胶质细胞瘤。目前,这些肿瘤的金标准诊断依赖于组织学分类;然而,在这些肿瘤中发现的新兴分子异常在肿瘤诊断过程中,以及因此在患者管理中发挥着越来越重要的作用。肿瘤蛋白 p53(TP53)异常、涉及 1p 和 19q 染色体缺失、O(6)-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子甲基化状态、PTEN 肿瘤抑制基因和 BRAF 癌基因异常以及异柠檬酸脱氢酶(IDH)突变的频率和临床重要性已经得到更好的定义。分子标志物在决定低级别神经胶质瘤患者的治疗过程中,历史上并没有重要作用,但正在进行的 III 期临床试验纳入了 1p 缺失或 1p19q 联合缺失状态,未来的试验计划将纳入 MGMT 启动子甲基化状态作为分层因素。未来的试验将需要将 IDH 突变状态纳入这些因素。最终,分子标志物评估有望提高肿瘤诊断的准确性,并增强治疗效果,从而改善患者预后。

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