Bahcesehir University, School of Medicine, Department of Medical Biology, Istanbul, Turkey.
Turk Neurosurg. 2021;31(4):587-593. doi: 10.5137/1019-5149.JTN.33347-20.2.
To elucidate the association of the MTHFR, MTRR, and RAD54L gene variations with meningioma in Turkish cohort.
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.
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).
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.
阐明 MTHFR、MTRR 和 RAD54L 基因变异与土耳其队列脑膜瘤的关联。
从 87 例回顾性脑膜瘤样本中分离 DNA。使用特定引物通过聚合酶链反应 (PCR) 扩增 MTHFR、MTRR 和 RAD54L 基因热点区域，并进行下一代测序 (NGS)。列出并比较所有检测到的变异和单核苷酸多态性 (SNP) 与不同基因组数据库中健康对照的频率。比较脑膜瘤的组织病理学特征和基因组变异。使用 Pearson χ 2 检验检测 SNP 的统计学差异，并进行相关性分析。
MTHFR 上的 rs1801131、rs1801133 和 rs4846051、MTRR 上的 rs1801394 和 RAD54L 基因上的 rs1048771 频率在 87 例脑膜瘤患者的总体队列中发现明显改变。脑膜瘤队列中 rs18011031 的频率为 0.09，与 WHO 肿瘤分级显著相关 (p = 0.038)。脑膜瘤队列中 rs18011033 的频率为 0.29，与 WHO 肿瘤分级显著相关 (p = 0.045)。此外，脑膜瘤队列中 rs4846051 的频率为 0.18，与 WHO 肿瘤分级显著相关 (p = 0.023)，与低 Ki67 增殖指数也显著相关 (p = 0.00455)。脑膜瘤队列中 rs1801394 的频率为 0.15，与 Ki67 增殖指数高显著相关 (p = 0.0144)。脑膜瘤队列中 rs1048771 的频率为 0.09，与肿瘤非坏死组织病理学形式显著相关 (p = 0.05)。
我们报告了叶酸代谢 (MTHFR、MTRR) 和 DNA 修复机制 (RAD54L) 基因的遗传改变与脑膜瘤组织病理学特征之间存在显著关联。在这些基因上发现了 5 个显著的 SNP 和 4 个 SNP 与组织病理学特征的显著相关性。这是一项初步的有前景的研究，旨在为土耳其队列的叶酸代谢和 DNA 修复基因建立脑膜瘤诊断和预后的遗传标记分析。
