Ellis H P, McInerney C E, Schrimpf D, Sahm F, Stupnikov A, Wadsley M, Wragg C, White P, Prise K M, McArt D G, Kurian K M
Brain Tumour Research Centre, University of Bristol, Bristol, UK.
Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
J Oncol. 2019 Dec 31;2019:4878547. doi: 10.1155/2019/4878547. eCollection 2019.
Glioblastoma is the most common primary adult brain tumour, and despite optimal treatment, the median survival is 12-15 months. Patients with matched recurrent glioblastomas were investigated to try to find actionable mutations. Tumours were profiled using a validated DNA-based gene panel. Copy number variations (CNVs) and single nucleotide variants (SNVs) were examined, and potentially pathogenic variants and clinically actionable mutations were identified. The results revealed that glioblastomas were -wildtype ( ; = 38) and -mutant ( ; = 3). SNVs in , , , , and were variants of unknown significance (VUS) that were predicted to be pathogenic in both subtypes. tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, WNT, SHH, NOTCH, Rb, and G-protein pathways. Many tumours had (18%) variants, including confirmed somatic mutations in haemangioblastoma. recurrent tumours had fewer pathways impacted (RTK/Ras/PI(3)K, p53, WNT, and G-protein) and CNV gains (, , and ) and losses ( and ). tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, and WNT pathways. VUS in was possibly pathogenic in . Recurrent tumours also had fewer pathways (p53, WNT, and G-protein) impacted by genetic alterations. Public datasets (TCGA and GDC) confirmed the clinical significance of findings in both subtypes. Overall in this cohort, potentially actionable variation was most often identified in , , , and . This study underlines the need for detailed molecular profiling to identify individual GBM patients who may be eligible for novel treatment approaches. This information is also crucial for patient recruitment to clinical trials.
胶质母细胞瘤是最常见的原发性成人脑肿瘤，尽管进行了最佳治疗，中位生存期仍为12 - 15个月。对复发性胶质母细胞瘤匹配的患者进行了研究，以试图找到可操作的突变。使用经过验证的基于DNA的基因检测板对肿瘤进行分析。检查了拷贝数变异（CNV）和单核苷酸变异（SNV），并鉴定了潜在的致病变异和临床可操作的突变。结果显示，胶质母细胞瘤为野生型（；= 38）和突变型（；= 3）。、、、和中的SNV是意义未明的变异（VUS），预计在两种亚型中均具有致病性。肿瘤具有影响RTK/Ras/PI(3)K、p53、WNT、SHH、NOTCH、Rb和G蛋白通路的SNV。许多肿瘤有（18%）变异，包括成血管细胞瘤中已确认的体细胞突变。复发性肿瘤影响的通路较少（RTK/Ras/PI(3)K、p53、WNT和G蛋白），CNV增益（、和）和缺失（和）也较少。肿瘤具有影响RTK/Ras/PI(3)K、p53和WNT通路的SNV。中的VUS在中可能具有致病性。复发性肿瘤受基因改变影响的通路也较少（p53、WNT和G蛋白）。公共数据集（TCGA和GDC）证实了两种亚型研究结果的临床意义。总体而言，在该队列中，潜在的可操作变异最常出现在、、、和中。这项研究强调了进行详细分子分析以识别可能适合新治疗方法的个体胶质母细胞瘤患者的必要性。这些信息对于患者纳入临床试验也至关重要。
