TET2 Promoter DNA Methylation and Expression Analysis in Pediatric B-cell Acute Lymphoblastic Leukemia.
TET2 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 was found in human cancer. Previous analysis revealed no TET2 mutations in acute lymphoblastic leukemia (ALL). Since the TET2 promoter methylation status in pediatric ALL has not been reported, the aim of the present study was to determine if promoter hypermethylation may be a mechanism of TET2 inactivation in a group of pediatric ALL cases. Methylation of TET2 promoter region in one (1/45) ALL B-common patient was detected by methylation specific polymerase chain reaction (PCR) and subsequently analyzed by bisulfite sequencing. We found no correlation between promoter methylation and gene expression, measured by quantitative reverse transcriptase-PCR, however the level of TET2 expression in ALL group was significantly decreased compared to children's normal peripheral blood mononuclear cells and isolated B-cells. TET2 promoter hypermethylation seems to have limited clinical relevance in childhood B-cell ALL due to its low frequency.
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Warsaw, Poland.
Ewa
E
Musialik
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Warsaw, Poland.
Mateusz
M
Bujko
Department of Pediatric Haematology and Oncology, Medical University of Warsaw , Poland.
Agnieszka
A
Wypych
Department of Pediatric Haematology and Oncology, Medical University of Warsaw , Poland.
Michał
M
Matysiak
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Warsaw, Poland.
Janusz Aleksander
JA
Siedlecki
B-cell acute lymphoblastic leukemia; DNA methylation; TET2