title: Tumor suppressor gene methylation on the short arm of chromosome 1 in chronic myelogenous leukemia.
abstract: OBJECTIVE
  We previously reported loss of heterozygosity on 1p in chronic myelogenous leukemia (CML). We analyzed promoter methylation and mutation of tumor suppressor genes on 1p36 in CML.
  
  
  METHODS
  We performed methylation-specific PCR (MS-PCR) analysis of the PRDM2, RUNX3, and TP73 genes in 61 patients with CML (43 chronic phase, CP; two accelerated phase; and 16 blast crisis, BC). Oxidative MS-PCR, PCR-single-strand conformation polymorphism, and real-time reverse transcriptase PCR were also analyzed. K-562 cells were grown in the presence of 5-Aza-dC and trichostatin A.
  
  
  RESULTS
  Methylation of the PRDM2, RUNX3, and TP73 genes was detected in 24/60 (40%), 21/61 (34%), and 28/60 (47%) patients, respectively. Methylation of all three genes was detected in 19/59 (32%) patients. Methylation was more frequent in BC than in CP. Oxidative MS-PCR analysis detected 5-mC in the PRDM2, RUNX3, and TP73 genes in 10/22 (45%), 15/21 (71%), and 16/26 (62%) samples with methylation detected by MS-PCR, respectively. Decreased expression was observed in several samples with methylation, while no mutations were found in the genes. Treatment of K-562 cells induced growth suppression, demethylation, and reexpression of the PRDM2 and RUNX3 genes.
  
  
  CONCLUSIONS
  Multiple tumor suppressor genes on 1p were inactivated in CML by methylation.
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Naoki
authors.identifier: http://orcid.org/0000-0002-4176-6120
authors.initials: N
authors.lastname: Mori
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Ohwashi-Miyazaki
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshinaga
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiseki
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Motoji
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002878:Chromosomes, Human, Pair 1; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D000072160:Tumor Protein p73 / Q000235:genetics
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000072160:Tumor Protein p73; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human
keywords: molecular cytogenetics; myeloproliferative neoplasms