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胶质瘤的预测和预后因素。

Predictive and prognostic factors for gliomas.

机构信息

Hôpital Neurologique, Service de Neurologie B, Lyon, France.

出版信息

Expert Rev Anticancer Ther. 2011 May;11(5):781-9. doi: 10.1586/era.10.202.

Abstract

Despite recent therapeutic advances, gliomas, in particular the most frequent and malignant glioblastoma, remain devastating tumors and need a better molecular characterization to improve both classification and treatment. Currently, three molecular markers, related to better outcome, are particularly useful and complement the histological classification: the 1p/19q codeletion strongly predicts prolonged response to treatment and prolonged survival in oligodendroglial tumors; the O(6)-methylguanine-DNA methyltransferase promoter methylation, which is hypothesized to render the cell more vulnerable to alkylants, is associated with a stronger benefit of concomitant chemoradiotherapy in glioblastomas; mutations of the IDH1 (more rarely IDH2) gene affects 40% of gliomas (but 100% of the 1p/19q codeleted gliomas) and is inversely correlated to grade. IDH1 mutation is a strong and independent predictor of survival, whatever grade considered. The consequences of IDH1/IDH2 mutation (that results in a new enzymatic activity transforming alphacetoglutarate into 2-hydroxyglutarate) are currently under investigation. Recently, integrated genomic, transcriptomic and epigenetic studies have unraveled new glioblastoma subgroups that further refines the molecular classification of these tumors. Such an approach should be extended to lower grade gliomas.

摘要

尽管最近有了治疗上的进展,但神经胶质瘤,尤其是最常见和最恶性的胶质母细胞瘤,仍然是具有破坏性的肿瘤,需要更好的分子特征来改善分类和治疗。目前,有三个与更好的预后相关的分子标志物,特别有用并补充了组织学分类:1p/19q 缺失强烈预测少突胶质细胞瘤对治疗的反应和生存时间延长;O(6)-甲基鸟嘌呤-DNA 甲基转移酶启动子甲基化,据推测使细胞对烷化剂更敏感,与胶质母细胞瘤同期放化疗的获益更强相关;IDH1(更罕见的 IDH2)基因突变影响 40%的神经胶质瘤(但 100%的 1p/19q 缺失的神经胶质瘤),与级别呈负相关。无论考虑哪个级别,IDH1 突变都是生存的强烈且独立的预测因子。IDH1/IDH2 突变(导致新的酶活性将α-酮戊二酸转化为 2-羟基戊二酸)的后果目前正在研究中。最近,综合基因组、转录组和表观遗传研究揭示了新的胶质母细胞瘤亚组,进一步完善了这些肿瘤的分子分类。这种方法应该扩展到低级别神经胶质瘤。

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