Overlapping variants in the blood, tissues and cell lines for patients with intracranial meningiomas are predominant in stem cell-related genes
Deema Hussein,
Ashraf Dallol,
Rita Quintas,
Hans-Juergen Schulten,
Mona Alomari,
Saleh Baeesa,
Mohammed Bangash,
Fahad Alghamdi,
Ishaq Khan,
M-Zaki Mustafa ElAssouli,
Mohamad Saka,
Angel Carracedo,
Adeel Chaudhary,
Adel Abuzenadah
Affiliations
Deema Hussein
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; Corresponding author.
Ashraf Dallol
Centre of Innovation for Personalized Medicine, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Rita Quintas
Galician Foundation of Genomic Medicine-SERGAS, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain
Hans-Juergen Schulten
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Mona Alomari
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
Saleh Baeesa
Division of Neurosurgery, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Mohammed Bangash
Division of Neurosurgery, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Fahad Alghamdi
Pathology Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Ishaq Khan
Institute of Basic Medical Sciences, Khyber Medical University, Peshawar 25100, Pakistan
M-Zaki Mustafa ElAssouli
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
Mohamad Saka
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
Angel Carracedo
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Galician Foundation of Genomic Medicine-SERGAS, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain
Adeel Chaudhary
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; Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Adel Abuzenadah
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; Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Objective: 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. Method: 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. Results: 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, GPRIN2, ALDH3B2, ASPN, THSD7A and SIGLEC6, 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 RUNX2 and CCDC114 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 NCOA3/AIB1/SRC3 as the most frequent BTC gene. Further analysis of the possible impact of the poly-Q mutation present in the NCOA3 gene indicated associated deregulation of 15 genes, including the up-regulation of the stem cell related SEMA3D gene and the angiogenesis related VEGFA gene. Conclusion: 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.
