Introduction

Glioblastoma (GBM) is an aggressive brain tumor associated with high degree of resistance to treatment. Given its heterogeneity, it is important to understand the molecular landscape of this tumor for the development of more effective therapies. Because of the different genetic profiles of patients with GBM, we sought to identify genetic variants in Lebanese patients with GBM (LEB-GBM) and compare our findings to those in the Cancer Genome Atlas (TCGA).

Methods

We performed whole exome sequencing (WES) to identify somatic variants in a cohort of 60 patient-derived GBM samples. We focused our analysis on 50 commonly mutated GBM candidate genes and compared mutation signatures between our population and publicly available GBM data from TCGA. We also cross-tabulated biological covariates to assess for associations with overall survival, time to recurrence and follow-up duration.

Results

We included 60 patient-derived GBM samples from 37 males and 23 females, with age ranging from 3 to 80 years (mean and median age at diagnosis were 51 and 56, respectively). Recurrent tumor formation was present in 94.8% of patients (n = 55/58). After filtering, we identified 360 somatic variants from 60 GBM patient samples. After filtering, we identified 360 somatic variants from 60 GBM patient samples. Most frequently mutated genes in our samples included ATRX, PCDHX11, PTEN, TP53, NF1, EGFR, PIK3CA, and SCN9A. Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). EGFR and NF1 mutations were associated with the frontal lobe and temporal lobe in our LEB-GBM cohort, respectively.

Conclusions

Our WES analysis confirmed the similarity in mutation signature of the LEB-GBM population with TCGA cohorts. It showed that 1 out of the 50 commonly GBM candidate gene mutations is associated with decreased overall survival among the Lebanese cohort. This study also highlights the need for studies with larger sample sizes to inform clinicians for better prognostication and management of Lebanese patients with GBM.

中文翻译：

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全外显子组测序的遗传改变与黎巴嫩胶质母细胞瘤患者临床结局的相关性

介绍

胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，与高度的治疗抵抗力相关。鉴于其异质性，重要的是了解这种肿瘤的分子结构，以开发更有效的疗法。由于GBM患者的遗传特征不同，我们试图鉴定黎巴嫩GBM患者（LEB-GBM）的遗传变异并将我们的发现与癌症基因组图谱（TCGA）进行比较。

方法

我们进行了全外显子组测序（WES），以鉴定60个患者来源的GBM样本队列中的体细胞变异。我们将分析重点放在了50个通常突变的GBM候选基因上，比较了我们的人群与TCGA公开提供的GBM数据之间的突变特征。我们还对生物协变量进行了列表分析，以评估其与总生存期，复发时间和随访时间的相关性。

结果

我们纳入了60例患者来源的GBM样本，分别来自37位男性和23位女性，年龄在3至80岁之间（诊断时的平均年龄和中位年龄分别为51岁和56岁）。94.8％的患者存在复发性肿瘤形成（n = 55/58）。过滤后，我们从60个GBM患者样本中鉴定出360个体细胞变异。过滤后，我们从60个GBM患者样本中鉴定出360个体细胞变异。在我们的样本中最常见的突变基因包括ATRX，PCDHX11，PTEN，TP53，NF1，EGFR，PIK3CA和SCN9A。NLRP5中的突变与黎巴嫩GBM人群的总体生存率下降相关（p = 0.002）。NLGB5中的突变与黎巴嫩GBM人群的总体生存率降低有关（p = 0.002）。在我们的LEB-GBM队列中，EGFR和NF1突变分别与额叶和颞叶相关。

结论

我们的WES分析证实了LEB-GBM人群与TCGA队列的突变特征相似。结果表明，黎巴嫩人群中50个常见的GBM候选基因突变中有1个与总体存活率下降有关。这项研究还强调了需要进行更大样本量的研究，以告知临床医生更好地对黎巴嫩GBM患者进行预后和治疗。