多惺惺惺惺胶质细胞瘤(GBM).ppt

多形性胶质母细胞瘤（Glioblastoma multiforme，GBM） 一.GBM简介 二.GBM的分类 三 .GBM core pathways 1.EGFR/PTEN/Akt/mTOR Pathway NF1 is a human glioblastoma suppressor gene Somatic mutations of the PI(3)K complex in human glioblastoma 2.TP53/MDM2/p14ARF Pathway 3. p16INK4a/RB1 Pathway 四 . LOH：Loss of Heterozygosity 五. Promoter Methylation 六 . 主要参考文献 * * GBM是一种生长迅速且致死率极高的脑部恶性脑瘤，多见于45~70岁的成年人。GBM好发于额叶、颞叶白质，浸润范围广，常可穿过胼胝体到对侧，呈蝴蝶状生长。根据CBTRUS统计，恶性胶质瘤约占原发性恶性脑肿瘤的70%。 年发病率约为5/100,000，每年新发病例超过14,000例。WHO将其定义为IV级疾病。 1.根据发病原因及临床表现 原发性GBM：发生于脑实质内，约占GBM的90%。多以原癌基因EGFR的扩增与过量表达为主。另外，10q杂合性丢失、p16INK4a缺失以及PTEN变异在原发性GBM中也有报道。~62岁。 继发性GBM：继发性胶质母细胞瘤多数由低级弥散性星形细胞瘤或间变性星形细胞瘤进一步恶变而来，多以p53基因的突变为主要表现，也存在10q杂合性丢失。 原发性GBM和继发性GBM在启动子的甲基化、RNA的表达模式以及蛋白质的表达水平也存在差异。~45岁。 2.根据基因表达模式分类 Classical subgroup： characterized by abnormally high levels of EGFR and none of TP53 mutations Proneural subgroup：characterized by having the most frequent mutations in the IDH1 、 TP53 and PDGFRA genes. The Proneural subgroup was significantly younger and they also tended to survive longer Mesenchymal subgroup：contains the most frequent number of mutations in the NF1 、 PTEN and TP53 Neural subgroup：characterized by the expression of several gene types that are also typical of the brain’s normal, noncancerous nerve cells, or neurons. 1.EGFR/PTEN/Akt/mTOR Pathway 2.TP53/MDM2/p14ARF Pathway 3.p16INK4a/RB1 Pathway is a key signaling pathway in the development of primary glioblastomas Amplification and overexpression of the EGFR EGFR variant 3 (EGFRvIII) with deletion of the extracellular domain （exons 2 to 7） PTEN inhibits the PIP3 signal R1391S R1513* e25-1 e29+1 Q1966* The PI(3)K complex consists of a catalytically active protein, p110a, encoded by PIK3CA, and a regulatory protein, p85a, encoded by PIK3R1. PIK3CA： ABD：adaptor binding domain L10del P17del M1043V C420R N345K R88Q PIK3R1：D560Y、N564K R574del、 T576del and W583del