Bahari Gholamreza, Hashemi Mohammad, Naderi Majid, Taheri Mohsen
Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran E-mail :
Asian Pac J Cancer Prev. 2016;17(8):3959-62.
The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our findings indicated that promoter methylation of TET2 significantly increases the risk of ALL (OR=2.60, 95% CI=1.31-5.12, p=0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was significantly downregulated in childhood ALL compared to healthy children (p=0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to confirm our findings.
十一易位蛋白2（TET2）基因是一种新型肿瘤抑制基因，与多种髓系和淋巴系起源的血液系统恶性肿瘤有关。除功能缺失突变和缺失外，在人类癌症中还发现TET2启动子处的CpG岛发生高甲基化。TET2编码的蛋白质调节DNA甲基化。本研究旨在检测伊朗东南部100例儿童急性淋巴细胞白血病（ALL）病例和120名健康儿童中TET2的DNA启动子甲基化情况。此外，还评估了30例新发ALL病例和32例对照的mRNA表达水平。我们的研究结果表明，与未发生甲基化相比，TET2启动子甲基化显著增加ALL风险（OR=2.60，95%CI=1.31-5.12，p=0.0060）。此外，与健康儿童相比，儿童ALL中TET2基因显著下调（p=0.0235）。结果显示，TET2基因的高甲基化和下调可能在儿童ALL的易感性中起作用。需要进一步开展更大样本量和不同种族的研究来证实我们的发现。
