BackgroundThe first histogenetic concepts favored dural origin of meningioma which was based on its dural attachment and thus meningiomais thought to arise from arachnoidal cap cells (meningiothelial) The micro environment which contains cancerous stem cell, is called cellular environment which is essential for tumor survival. Cancerous stem cell (CSC) is capable of initiating tumor growth and metastasis and stem cell marker are known to used by scientists to isolate and identify certain stem cell.This study aims to describe the stem cell markers CD44, CD73 and CD 105 in meningioma among Sudanese patients and to isolate cancerous stem cells (CSCs) from meningioma tissues samples and test its in-vivo growth in Albino-Wister rats Material and methodsThis is a prospective cross-sectional experimental study done at the National Center of Neurological Sciences (NCNS) Khartoum, from 2019 to 2021. All established cranial meningioma patients were included. Tumor specimens were processed for RNA extraction and PCR. Tumor specimens were processed for RNA extraction and PCR. Twelve tissue samples were further processed for stem cells isolation and identificationTumor genesis of the isolated CSCs was tested through in-vivo application of the cells on brains of Albino Wister rats. The animals were sacrificed 3 months later and slices of the fixed brains were stained with H&E and studied microscopically for histopathology verification of the growing cells and further confirmed by immune-histochemistry using epithelial membrane antigen and progesterone receptor as specific cell markers for meningioma.ResultsA total of 23 meningioma cases were enrolled in the study. All sample expressed CD44, but CD73 and CD 105 expression was variable not on the different subtype, but within the same type .Successful isolation of cultured cells with cardinal features of mesenchymal stem cells was obtained. The implanted cells showed tumor growth consistent histologically and immune-histochemicaly with meningioma.

Introduction Meningioma is the second most common primary intracranial tumor of the central nervous system. in Sudan, meningioma is the most common primary brain tumor, among Sudanese patients, Surgical total excision of meningioma offers a better survival, however, Chemotherapy has largely been unsuccessful for meningioma treatment, and therefore, refractory and recurrence meningioma treated with palliative surgery and radiotherapy. Monosomy of chromosome 22 is the utmost common genetic alteration among meningioma and many genes were investigated and described in the development of this tumor of which , NF2 hSNF5/INI1gene, P53. In addition to this, Molecular signal pathways in meningioma, and that contribute to the survival, proliferation, self-renewal, and differentiation properties of normal stem cells which are abnormally activated and nominated as cancerous stem cell (CSCs). Objectives 1/ To identify the possible pathway of candidate genes in both setting and whole genes hypothesis free approach 2/ To assess the presence of mutations in candidate genes among histological subtypes of meningioma in Sudan. Material and methods This is a prospective cross-sectional study done at the National Center of Neurological Sciences (NCNS) Khartoum, from 2018 to 2021. The study included all cerebral tumors that were radio- logically diagnosed preoperatively as meningioma. Ethical approval was taken from Institute of Endemic disease, Khartoum University, and written consent was obtained Three DNA extracts were randomly selected from 20 meningioma tissue samples and processed for WES. All genes harboring exonic and splice site variations stratified into SNVs and INDELs sets were prepared. The 1000G online database was used to explore novel mutations per 3 samples. SIFT and PolyPhen-2 programs were used to predict possible impact of amino acids substitution. To address meticulous genes interaction and particular centrality, all shared genes within the class INDEL and SNVs were used as input on Network Analysis to predict protein- protein interaction and functional gene ontology. Finally, shared mutations within genes of centrality were detected via Sanger sequencing and mutations were correlated between histological sub-types and recurrenceThree non meningioma brain tumor used as control. Results WES analysis revealed high number for mutational signature within 2 classes (INDEL and SNVs) per 3 samples, the findings of 1000 genome online database showed number of novel mutations; 5618 in fibrous , 6032 in meningothelial while in recurrent fibrous sample 5930. Network analysis of shared genes per each class (INDEL, SNVs), showed UBC is the most protein of remarkable degree centrality over thousand of genes. Whereas, all shared genes per 3 samples within the 2 classes (INDEL and SNVs) revealed Akt1 with the highest degree of centrality and betweenness. Akt1 rs17846829was detected in 20% of the samples, while CD44 stemness gene revealed mutation A>G (rs9666607) in all meningioma samples (100%), this mutation was associated with 60% of the recurrence. Conclusions Nevertheless, the present study, highlight how such complex molecular processes might contribute to tumorogenesis, in attempt to shed light over thousands of genes and multifaceted network analysis rather than a solitary gene which is challenging question.