Turkish Neurosurgery 2021 , Vol 31 , Num 4
Association of MTHFR, MTRR and RAD54L Gene Variations with Meningioma and Correlation with Tumor's Histopathological Characteristics on Turkish Cohort
Timucin AVSAR1,Rashid MOHIYUDDIN2,Seyma CALIS3,Ozlem YAPICIER5,Turker KILIC2
1Bahcesehir University, School of Medicine, Department of Medical Biology, Istanbul, Turkey
2Bahcesehir University, Health Sciences Institute, Neuroscience Program, Istanbul, Turkey
3Bahcesehir University, Health Sciences Institute, Neuroscience Laboratory, Istanbul, Turkey
4Istanbul Technical University, Engineering and Technology, Graduate School of Science, Molecular Biology, Genetics and Biotechnology Graduate Program, Istanbul, Turkey
5Bahcesehir University, School of Medicine, Department of Neurosurgery, Istanbul, Turkey
6Bahcesehir University, School of Medicine, Department of Pathology, Istanbul, Turkey
DOI : 10.5137/1019-5149.JTN.33347-20.2 AIM: To elucidate the association of the MTHFR, MTRR, and RAD54L gene variations with meningioma in Turkish cohort.

MATERIAL and METHODS: DNAs were isolated from 87 retrospective meningioma samples. The MTHFR, MTRR, and RAD54L gene hotspot regions were amplified with specific primers via polymerase chain reaction (PCR), and next-generation sequencing (NGS) was performed. All the detected variations and single-nucleotide polymorphisms (SNPs) were listed and compared with healthy control frequencies in different genomic databases. The histopathological characteristics of meningiomas and genomic variations were compared. Pearson?s chi-squared test was used to detect the statistical differences of SNPs, and correlation analysis was conducted.

RESULTS: rs1801131, rs1801133, and rs4846051 on MTHFR, rs1801394 on MTRR, and rs1048771 on RAD54L gene frequencies were found to be significantly altered in the overall cohort of 87 patients with meningioma. The frequency of rs18011031 is 0.09 in the meningioma cohort, which is significantly correlated with WHO tumor grades (p = 0.038). The frequency of rs18011033 is 0.29 in the meningioma cohort, which is significantly correlated with WHO tumor grades (p = 0.045). Furthermore, the frequency of rs4846051 is 0.18 in the meningioma cohort, which is significantly correlated with WHO tumor grades (p = 0.023) and also with low Ki67 proliferation index (p = 0.00455). The frequency of rs1801394 is 0.15 and significantly associated with high Ki67 proliferation index in the meningioma cohort (p = 0.0144). The frequency of rs1048771 is 0.09 in the meningioma cohort and is significantly associated with the non-necrotic histopathological form of the tumor (p = 0.05).

CONCLUSION: We reported a significant association between the genetic alterations of folate metabolism (MTHFR, MTRR) and DNA repair mechanism (RAD54L) genes with the histopathological characteristics of meningioma. Five significant SNPs on these genes and four significant correlations of SNPs with histopathological characteristics were identified. This is a preliminary promising study conducted to establish the genetic marker analysis for meningioma diagnosis and prognosis for folate metabolism and DNA repair genes in Turkish cohort. Keywords : Meningioma, Histopathology, Genetic markers, Folate metabolism genes, DNA repair genes

Corresponding author : Timucin AVSAR, timucin.avsar@med.bau.edu.tr