Lin Lei, Wang Bo, Zhang Xinxin, Deng Changmi, Zhou Chunlei, Zhu Jinhong, Wu Haiyan, He Jing
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Department of Clinical Laboratory, Qingdao Eighth People's Hospital, Qingdao, Shandong, China.
IUBMB Life. 2024 Apr;76(4):200-211. doi: 10.1002/iub.2791. Epub 2023 Nov 28.
The 5-methylcytosine (m5C) is the key chemical modification in RNAs. As one of the demethylases in m5C, TET2 has been shown as a tumor suppressor. However, the impact of TET2 gene polymorphisms on neuroblastoma has not been elucidated. 402 neuroblastoma patients and 473 controls were genotyped for TET2 gene polymorphisms using the TaqMan method. The impact of TET2 gene polymorphisms on neuroblastoma susceptibility was determined using multivariate logistic regression analysis. We also adopted genotype-tissue expression database to explore the impact of TET2 gene polymorphisms on the expression of host and nearby genes. We used the R2 platform and Sangerbox tool to analyze the relationship between gene expression and neuroblastoma risk and prognosis through non-parametric testing and Kaplan-Meier analysis, respectively. We found the TET2 gene polymorphisms (rs10007915 G > C and rs7670522 A > C) and the combined 2-5 risk genotypes can significantly increase neuroblastoma risk. Stratification analysis showed that these significant associations were more prominent in certain subgroups. TET2 rs10007915 G > C and rs7670522 A > C are significantly associated with reduced expression of TET2 mRNA. Moreover, lower expression of TET2 gene is associated with high risk, MYCN amplification, and poor prognosis of neuroblastoma. The rs10007915 G > C and rs7670522 A > C are significantly related to the increased expression of inorganic pyrophosphatase 2 mRNA, and higher expression of PPA2 gene is associated with high risk, MYCN amplification, and poor prognosis of neuroblastomas. In summary, TET2 rs10007915 G > C and rs7670522 A > C significantly confer neuroblastoma susceptibility, and further research is needed to investigate the underlying mechanisms.
5-甲基胞嘧啶（m5C）是RNA中的关键化学修饰。作为m5C中的去甲基化酶之一，TET2已被证明是一种肿瘤抑制因子。然而，TET2基因多态性对神经母细胞瘤的影响尚未阐明。采用TaqMan方法对402例神经母细胞瘤患者和473例对照进行TET2基因多态性基因分型。使用多因素逻辑回归分析确定TET2基因多态性对神经母细胞瘤易感性的影响。我们还采用基因型-组织表达数据库来探讨TET2基因多态性对宿主基因和邻近基因表达的影响。我们分别使用R2平台和Sangerbox工具，通过非参数检验和Kaplan-Meier分析来分析基因表达与神经母细胞瘤风险和预后之间的关系。我们发现TET2基因多态性（rs10007915 G＞C和rs7670522 A＞C）以及合并的2-5种风险基因型可显著增加神经母细胞瘤风险。分层分析表明，这些显著关联在某些亚组中更为突出。TET2 rs10007915 G＞C和rs7670522 A＞C与TET2 mRNA表达降低显著相关。此外，TET2基因低表达与神经母细胞瘤的高风险、MYCN扩增和不良预后相关。rs10007915 G＞C和rs
