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Abstract：
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. This cancer shows rapid, highly infiltrative growth, that invades individually or in small groups the surrounding tissue. The aggressive tumor biology of GBM has devastating consequences with a median survival of 15 months. GBM often has Epidermal Growth Factor Receptor (EGFR) abnormalities. Despite recent advances in the study of GBM tumor biology, it is unclear whether mutations in GBM are related to EGFR amplification and relevant phenotypes like tumor infiltration. This study aimed to perform whole-exome sequencing analysis in 30 human GBM samples for identifying mutational portraits associated with EGFR amplification and infiltrative patterns. Our results show that EGFR-amplified tumors have overall higher mutation rates than EGFR-no-amplified. Six genes out of 2029 candidate genes show mutations associated with EGFR amplification status. Mutations in these genes for GBM are novel, not previously reported in GBM, and with little presence in the TCGA database. GPR179, USP48, and BLK show mutation only in EGFR-amplified cases, and all the affected cases exhibit diffuse infiltrative patterns. On the other hand, mutations in ADGB, EHHADH, and PTPN13, were present only in the EGFR-no-amplified group with a more diverse infiltrative phenotype. Overall, our work identified different mutational portraits of GBM related to well-established features like EGFR amplification and tumor infiltration.
摘要：
胶质母细胞瘤(GBM)是成人最常见的恶性原发性脑肿瘤。这种癌症表现得很快，高度渗透生长，单独或成群侵入周围组织。GBM的侵袭性肿瘤生物学具有破坏性后果，中位生存期为15个月。GBM通常具有表皮生长因子受体(EGFR)异常。尽管GBM肿瘤生物学的研究取得了新进展，目前尚不清楚GBM中的突变是否与EGFR扩增和相关表型如肿瘤浸润相关.本研究旨在在30个人类GBM样品中进行全外显子组测序分析，以鉴定与EGFR扩增和浸润模式相关的突变肖像。我们的结果表明，EGFR扩增的肿瘤比未扩增的EGFR具有更高的突变率。2029个候选基因中的6个基因显示与EGFR扩增状态相关的突变。这些GBM基因的突变是新的，以前没有在GBM中报道过，并且在TCGA数据库中很少存在。GPR179、USP48和BLK仅在EGFR扩增病例中显示突变，所有受影响的病例都表现出弥漫性渗透模式。另一方面,ADGB中的突变，Ehhadh,和PTPN13仅存在于无EGFR扩增组,具有更多样化的浸润表型.总的来说,我们的工作确定了GBM的不同突变特征,这些突变特征与EGFR扩增和肿瘤浸润相关.
