Identification of novel genomic regions with aberrant cytosine methylation in hematological malignancies

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概要

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• 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.

著者

• Shinojima Yui

  Division Of Cancer Genetics Department Of Advanced Medical Science Nihon University School Of Medici

• Kobayashi Yujin

  Department Of Cardiology Nihon University School Of Medicine

• Nagase Hiroki

  Division Of Cancer Genetics Department Of Advanced Medical Research Center Nihon University School O

• Fujiwara Kyoko

  Division Of Cancer Genetics Department Of Advanced Medical Research Center Nihon University School O

• Soma Masayoshi

  Division Of General Medicine Department Of Internal Medicine Nihon University School Of Medicine

• Hatta Yoshihiro

  Department Of Hematology And Rheumatology Nihon University School Of Medicine

• Takeuchi Jin

  Department Of Hematology And Rheumatology Division Of Medicine Nihon University School Of Medicine

• Kawashima Hiroyuki

  Department Of Medicinal Chemistry Kyoto Pharmaceutical University

• Hatta Yoshihiro

  Department of Hematology and Rheumatology, Nihon University School of Medicine

• Igarashi Jun

  Division of General Medicine, Department of Medical, Nihon University School of Medicine

• Soma Masayoshi

  Division of General Medicine, Department of Medical, Nihon University School of Medicine

• Shinojima Yui

  Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine

• Nagase Hiroki

  Division of Cancer Genetics, Department of Advanced Medical Research Center, Nihon University School of Medicine

• Kawashima Hiroyuki

  Department of Chemistry, Faculty of Science, Hiroshima University

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