Glioma Biology and Molecular Markers
Glioma Biology and Molecular Markers
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DOI：
10.1007/978-3-319-12048-5_2
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Colman, Howard
中科院分区：
文献类型：
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作者：
Cohen, Adam L.;Colman, Howard
归类为胶质瘤的肿瘤包括多种组织学类型，包括较常见的（星形细胞瘤、胶质母细胞瘤）以及较不常见的组织学类型（少突胶质细胞瘤、混合性少突星形细胞瘤、毛细胞性星形细胞瘤）。最近在各种原发性脑肿瘤类型的综合遗传表征方面的努力已经确定了多种肿瘤类型共有的一些常见改变和途径。神经胶质瘤生物学中的常见途径包括生长因子受体酪氨酸激酶及其经由MAP激酶级联或PI 3 K信号传导的下游信号传导、经由p53的凋亡丧失、细胞周期调节、经由VEGF信号传导的血管生成和侵袭。然而，除了这些常见的一般途径改变之外，还在特定的肿瘤类型中鉴定了许多特定的改变，并且其中许多具有直接的治疗意义。这些包括在毛细胞型星形细胞瘤（和神经节细胞胶质瘤）中观察到的BRAF基因突变或融合。在少突胶质细胞瘤中，IDH 1突变和染色体1 p和19 q的共缺失与前期使用联合化疗和放疗的生存率提高相关，这些肿瘤也具有CIC和FUBP 1基因的独特突变。低级别胶质瘤越来越多地被视为基于IDH突变状态分为两组，星形细胞瘤通过IDH突变随后p53突变发展，而预后不良的低级别胶质瘤和原发性胶质母细胞瘤（GBM）的特征在于EGFR扩增、PTEN缺失和细胞周期蛋白依赖性激酶抑制剂缺失。GBM可以基于基因表达和基因甲基化模式进一步表征为三个或四个不同的亚组。弥漫性胶质瘤的预后标志物包括IDH突变、1 p/19 q共缺失和MGMT甲基化，MGMT也是接受替莫唑胺单药治疗的胶质母细胞瘤老年患者的预测标志物。
The tumors classified as gliomas include a wide variety of histologies including the more common (astrocytoma, glioblastoma), as well as the less common histologies (oligodendroglioma, mixed oligoastrocytoma, pilocytic astrocytoma). Recent efforts at comprehensive genetic characterization of various primary brain tumor types have identified a number of common alterations and pathways common to multiple tumor types. Common pathways in glioma biology include growth factor receptor tyrosine kinases and their downstream signaling via the MAP kinase cascade or PI3K signaling, loss of apoptosis through p53, cell cycle regulation, angiogenesis via VEGF signaling, and invasion. However, in addition to these common general pathway alterations, a number of specific alterations have been identified in particular tumor types, and a number of these have direct therapeutic implications. These include mutations or fusions in the BRAF gene seen in pilocytic astrocytomas (and gangliogliomas). In oligodendrogliomas, mutations in IDH1 and codeletion of chromosomes 1p and 19q are associated with improved survival with upfront use of combined chemotherapy and radiation, and these tumors also have unique mutations of CIC and FUBP1 genes. Low grade gliomas are increasingly seen to be divided into two groups based on IDH mutation status, with astrocytomas developing through IDH mutation followed by p53 mutation, while poor prognosis low grade gliomas and primary glioblastomas (GBMs) are characterized by EGFR amplification, loss of PTEN, and loss of cyclin-dependent kinase inhibitors. GBMs can be further characterized based on gene expression and gene methylation patterns into three or four distinct subgroups. Prognostic markers in diffuse gliomas include IDH mutation, 1p/19q codeletion, and MGMT methylation, and MGMT is also a predictive marker in elderly patients with glioblastoma treated with temozolomide monotherapy.