title: TET2 Promoter DNA Methylation and Expression in Childhood Acute Lymphoblastic Leukemia.
abstract: 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.
authors.affiliation: Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran E-mail : mhd.hashemi@gmail.com, hashemim@zaums.ac.ir.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Bahari
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.forename: Majid
authors.initials: M
authors.lastname: Naderi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Taheri
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D049308:Dioxygenases; C541081:TET2 protein, human