Hussein Deema, Dallol Ashraf, Quintas Rita, Schulten Hans-Juergen, Alomari Mona, Baeesa Saleh, Bangash Mohammed, Alghamdi Fahad, Khan Ishaq, ElAssouli M-Zaki Mustafa, Saka Mohamad, Carracedo Angel, Chaudhary Adeel, Abuzenadah Adel
Neurooncology Translational Group, King Fahd Medical Research Center, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Saudi Arabia.
Centre of Innovation for Personalized Medicine, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Heliyon. 2020 Nov 30;6(11):e05632. doi: 10.1016/j.heliyon.2020.e05632. eCollection 2020 Nov.
Bulk tissue genomic analysis of meningiomas identified common somatic mutations, however, it often excluded blood-related variants. In contrast, genomic characterisation of primary cell lines that can provide critical information regarding growth and proliferation, have been rare. In our work, we identified the variants that are present in the blood, tissues and corresponding cell lines that are likely to be predictive, tumorigenic and progressive.
Whole-exome sequencing was used to identify variants and distinguish related pathways that exist in 42 blood, tissues and corresponding cell lines (BTCs) samples for patients with intracranial meningiomas. Conventional sequencing was used for the confirmation of variants. Integrative analysis of the gene expression for the corresponding samples was utilised for further interpretations.
In total, 926 BTC variants were detected, implicating 845 genes. A pathway analysis of all BTC genes with damaging variants indicated the 'cell morphogenesis involved in differentiation' stem cell-related pathway to be the most frequently affected pathway. Concordantly, five stem cell-related genes, , , , and , showed BTC variants in at least five of the patients. Variants that were heterozygous in the blood and homozygous in the tissues or the corresponding cell lines were rare (average: 1.3 ± 0.3%), and included variants in the and genes An analysis comparing the variants detected only in tumours with aggressive features indicated a total of 240 BTC genes, implicating the 'homophilic cell adhesion via plasma membrane adhesion molecules' pathway, and identifying the stem cell-related transcription coactivator as the most frequent BTC gene. Further analysis of the possible impact of the poly-Q mutation present in the gene indicated associated deregulation of 15 genes, including the up-regulation of the stem cell related gene and the angiogenesis related gene
Stem cell-related pathways and genes showed high prevalence in the BTC variants, and novel variants in stem cell-related genes were identified for meningioma. These variants can potentially be used as predictive, tumorigenic and progressive biomarkers for meningioma.
脑膜瘤的大块组织基因组分析确定了常见的体细胞突变，然而，它通常排除了与血液相关的变异。相比之下，能够提供有关生长和增殖关键信息的原代细胞系的基因组特征分析却很少见。在我们的研究中，我们确定了存在于血液、组织及相应细胞系中的变异，这些变异可能具有预测性、致瘤性和进展性。
采用全外显子组测序来识别变异，并区分42例颅内脑膜瘤患者的血液、组织及相应细胞系（BTCs）样本中存在的相关通路。采用传统测序来确认变异。对相应样本的基因表达进行综合分析以作进一步解读。
共检测到926个BTC变异，涉及845个基因。对所有具有有害变异的BTC基因进行通路分析表明，“参与分化的细胞形态发生”干细胞相关通路是受影响最频繁的通路。相应地，五个干细胞相关基因，即 、 、 、 和 ，在至少五名患者中显示出BTC变异。在血液中为杂合子而在组织或相应细胞系中为纯合子的变异很少见（平均：1.3±0.3%），包括 和 基因中的变异。一项比较仅在具有侵袭性特征的肿瘤中检测到的变异的分析表明，共有240个BTC基因，涉及“通过质膜粘附分子的嗜同性细胞粘附”通路，并确定干细胞相关转录共激活因子 为最常见的BTC基因。对 基因中存在的多聚谷氨酰胺突变的可能影响进行的进一步分析表明，有15个基因发生相关失调，包括干细胞相关基因 的上调和血管生成相关基因 的上调。
干细胞相关通路和基因在BTC变异中具有高发生率，并且为脑膜瘤鉴定出了干细胞相关基因中的新变异。这些变异有可能用作脑膜瘤的预测性、致瘤性和进展性生物标志物。
