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 |
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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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