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[胶质瘤的分类。当前进展与展望]

[Classification of gliomas. Current progress and perspectives].

作者信息

Capper D, Reifenberger G

机构信息

Abteilung Neuropathologie, Universitätsklinikum Heidelberg und Deutsches Konsortium für Translationale Krebsforschung (DKTK), Klinische KooperationseinheitNeuropathologie, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland,

出版信息

Nervenarzt. 2015 Jun;86(6):672, 674-6, 678-80, passim. doi: 10.1007/s00115-014-4223-3.

Abstract

The diagnostic subdivision of gliomas is traditionally based on histological features as defined by the World Health Organization (WHO) classification of tumors of the central nervous system. In recent years molecular studies have identified a number of genetic and epigenetic markers that could contribute to an improved tumor classification and better prediction of response to therapy and prognosis in the individual patient. The most important molecular tests with differential diagnostic relevance in patients with astrocytic and oligodendroglial tumors include the detection of genetic mutations in the isocitrate dehydrogenase 1 (IDH1), IDH2, alpha thalassemia/mental retardation syndrome X-linked (ATRX), histone H3.3 (H3F3A) and v-raf murine sarcoma viral oncogene homolog B (BRAF) genes as well as the demonstration of codeletions of chromosomal arms 1p and 19q. Important predictive markers that have been linked to the response to alkylating chemotherapy are O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients and 1p/19q codel status in anaplastic glioma patients. Oncogenic c11orf95/RELA fusion gene formation is characteristic for a subgroup of patients with supratentorial ependymoma. In addition to diagnostic testing of individual genes, novel microarray and next generation sequencing (NGS) techniques show promising perspectives in glioma diagnostics. The assessment of DNA methylation profiles using DNA methylation arrays representing 450,000 CpG dinucleotides distributed throughout the human genome (450 k array test) now allows the robust molecular classification of gliomas into clinically relevant entities and variants. Moreover, glioma-associated gene panel NGS promises the timely parallel sequencing of relevant diagnostic and predictive marker genes in a single test. It will now be a major task to integrate these novel results and techniques into the conventional histological procedures in the up-coming revision of the WHO classification.

摘要

胶质瘤的诊断细分传统上基于世界卫生组织(WHO)中枢神经系统肿瘤分类所定义的组织学特征。近年来,分子研究已鉴定出一些遗传和表观遗传标志物,这些标志物有助于改进肿瘤分类,并更好地预测个体患者的治疗反应和预后。在星形细胞瘤和少突胶质细胞瘤患者中具有鉴别诊断意义的最重要分子检测包括检测异柠檬酸脱氢酶1(IDH1)、IDH2、α地中海贫血/智力发育迟缓综合征X连锁(ATRX)、组蛋白H3.3(H3F3A)和v-raf鼠肉瘤病毒癌基因同源物B(BRAF)基因中的基因突变,以及证明染色体臂1p和19q的共缺失。与烷化化疗反应相关的重要预测标志物是胶质母细胞瘤患者中的O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化和间变性胶质瘤患者中的1p/19q共缺失状态。致癌性c11orf95/RELA融合基因形成是幕上室管膜瘤患者亚组的特征。除了对单个基因进行诊断检测外,新型微阵列和下一代测序(NGS)技术在胶质瘤诊断中显示出有前景的前景。使用代表分布在整个人类基因组中的450,000个CpG二核苷酸的DNA甲基化阵列评估DNA甲基化谱(450k阵列测试)现在允许将胶质瘤进行可靠的分子分类为临床相关实体和变体。此外,胶质瘤相关基因panel NGS有望在一次检测中对相关诊断和预测标志物基因进行及时的平行测序。在即将到来的WHO分类修订版中把这些新结果和技术整合到传统组织学程序中将是一项主要任务。

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