title: Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype.
abstract: The cyclin-dependent kinase inhibitor p57(KIP2) is thought to be a potential tumor suppressor gene (TSG). The present study examines this possibility. We found that the expression of p57(KIP2) gene is absent in various hematological cell lines. Exposing cell lines to the DNA demethylating agent 5-aza-2'-deoxycytidine restored p57(KIP2) gene expression. Bisulfite sequencing analysis of its promoter region showed that p57(KIP2) DNA was completely methylated in cell lines that did not express the p57(KIP2) gene. Thus, DNA methylation of its promoter might lead to inactivation of the p57(KIP2) gene. DNA methylation of this region is thought to be an aberrant alteration, since DNA was not methylated in normal peripheral blood mononuclear cells or in reactive lymphadenitis. Methylation-specific polymerase chain reaction analysis found frequent DNA methylation of the p57(KIP2) gene in primary diffuse large B-cell lymphoma (54.9%) and in follicular lymphoma (44.0%), but methylation was infrequent in myelodysplastic syndrome and adult T-cell leukemia (3.0% and 2.0%, respectively). These findings directly indicate that the profile of the p57(KIP2) gene corresponds to that of a TSG.
authors.affiliation: First Department of Internal Medicine, and the First Department of Pathology, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Li
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagai
authors.forename: Toshihito
authors.initials: T
authors.lastname: Ohno
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yuge
authors.forename: Sonoko
authors.initials: S
authors.lastname: Hatano
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Mori
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Saito
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D050761:Cyclin-Dependent Kinase Inhibitor p57; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004273:DNA, Neoplasm; D009687:Nuclear Proteins