High-risk myelodysplastic syndromes and hypermethylation of the p15Ink4B gene.
Recent studies have elucidated that not only genetic alterations but also epigenetic changes may play an important role in carcinogenesis. In particular, de novo methylation of CpG islands within the promoter region associated with the inactivation of tumor suppressor genes (TSGs) has been demonstrated in various malignancies. Since de novo acute myelogenous leukemia shows frequent inactivation of the p15INK4B gene through the promoter methylation only, we investigated the methylation status of the p15INK4B gene in myelodysplastic syndrome (MDS). In MDS, the p15INK4B gene is also frequently hypermethylated at the promoter region located at the 5'-CpG island of exon 1. Association of frequent and strong methylation with high-risk MDS suggested that promoter methylation of the p15INK4B gene plays an important role as a late event during MDS progression. Since several TSGs and growth regulatory genes, including the p15INK4B gene, may be inactivated through promoter hypermethylation in hematological malignancies, modulation of the methylation status may be considered as a novel treatment modality in MDS.
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
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Uchida
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Kinoshita
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Hotta
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Murate
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D019175:DNA Methylation; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D012307:Risk Factors; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; D018844:Cyclin-Dependent Kinases