抄録
To identify novel hematologic tumor-specific differentially methylated regions, we performed DNA methylation analysis of 7 new candidate genes (ZAR1, GATA4, CDH22, SOX3, SLC16A5, EHD3 and TBPL1), which has been identified to be aberrantly methylated in human cancers or animal models of human cancer. Bone marrow or peripheral blood samples from 20 patients with leukemia (including 10 AML and 6 ALL) before treatment and normal lymphocyte cells from 4 healthy individuals as well as eight human leukemia/lymphoma cell lines were used in this study and analyzed with quantitative DNA methylation analysis using the Sequenom MassARRAY system. All four normal control samples showed no or very low level of cytosine methylation in all of the genomic regions examined. However, leukemia/lymphoma cell lines showed frequent hypermethylation of the ZAR1, SLC16A5, EDH3, GATA4, CDH22 and SOX3 genes. DNA hypermethylation of SOX3 was also frequently observed in most of hematologic malignancy cases. Aberrant hypermethylation of ZAR1, GATA4 and CDH22 was also frequently observed in both Philadelphia chromosome positive and negative ALL samples but not in all 10 AML cases. We identified novel genomic regions of ZAR1, GATA4, CDH22 and SOX3 with aberrant cytosine methylation in hematological malignancies. Among those, aberrant DNA methylation of ZAR1, GATA4 and CDH22 may be involved in carcinogenesis of lymphoid populations.
