Tumor suppressor gene methylation on the short arm of chromosome 1 in chronic myelogenous leukemia

Autor: Naoki Mori, Kentaro Yoshinaga, Michiko Okada, Mari Ohwashi-Miyazaki, Junji Tanaka, Toshiko Motoji, Masayuki Shiseki
Rok vydání: 2017
Předmět:
Adult
Male
0301 basic medicine
Tumor suppressor gene
Biology
Polymerase Chain Reaction
law.invention
Loss of heterozygosity
03 medical and health sciences
0302 clinical medicine
law
Cell Line
Tumor
Leukemia
Myelogenous
Chronic
BCR-ABL Positive
medicine
Humans
Genes
Tumor Suppressor
Genetic Predisposition to Disease
Promoter Regions
Genetic
Gene
Aged
Neoplasm Staging
Demethylation
Nuclear Proteins
Tumor Protein p73
Histone-Lysine N-Methyltransferase
Sequence Analysis
DNA
Hematology
General Medicine
Methylation
DNA Methylation
Middle Aged
medicine.disease
Molecular biology
DNA-Binding Proteins
Reverse transcription polymerase chain reaction
Core Binding Factor Alpha 3 Subunit
030104 developmental biology
Chromosomes
Human
Pair 1
Karyotyping
030220 oncology & carcinogenesis
Mutation
Suppressor
Female
Transcription Factors
Chronic myelogenous leukemia
Zdroj: European Journal of Haematology. 98:467-477
ISSN: 0902-4441
Popis: Objectives 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. Conclusion Multiple tumor suppressor genes on 1p were inactivated in CML by methylation.
Databáze: OpenAIRE
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