Asif Samia, Fatima Rawish, Krc Rebecca, Bennett Joseph, Raza Shahzad
Saint Luke's Cancer Institute, University of Missouri, Kansas City, MO 64111, USA.
CNS Oncol. 2019 Jun;8(2):CNS37. doi: 10.2217/cns-2019-0003. Epub 2019 Jul 10.
Glioblastoma multiforme (GBM) carries a dismal prognosis. Integrated proteogenomic analysis was performed to understand GBM pathophysiology. 17 patient samples were analyzed for driver mutations, oncogenes, major pathway alterations and molecular changes at gene and protein level. Clinical, treatment and survival data were collected. Significantly mutated genes included , , , , , and . EGFR mutations noted included EGFRvIII-expression, EGFR- missense mutation-exon 21 and EGFR fusion (FGFR3-TACC3). mutations were noticed in COSMIC hot-spot driver gene and accompany and mutations suggesting low- to high-grade glioma transformation. Proteomics showed higher (53%) EGFR expression than genomic expression (23%). MGMT methylation was present in two-thirds of cases. This study identifies a distinct biological process that may characterize each GBM differently. Proteogenomic data identify potential therapeutic targets of GBM.
多形性胶质母细胞瘤(GBM)预后不佳。进行了综合蛋白质基因组分析以了解GBM的病理生理学。对17例患者样本进行了驱动基因突变、癌基因、主要通路改变以及基因和蛋白质水平的分子变化分析。收集了临床、治疗和生存数据。显著突变的基因包括 、 、 、 、 、 和 。注意到的EGFR突变包括EGFRvIII表达、EGFR第21外显子错义突变以及EGFR融合(FGFR3-TACC3)。在COSMIC热点驱动基因中发现了 突变,并伴有 和 突变,提示低级别到高级别胶质瘤转化。蛋白质组学显示EGFR表达(53%)高于基因组表达(23%)。三分之二的病例存在MGMT甲基化。本研究确定了一个独特的生物学过程,该过程可能使每个GBM具有不同特征。蛋白质基因组数据确定了GBM的潜在治疗靶点。