| Epigenetic differences in cytogenetically normal versus abnormal acute myeloid leukemia. | |
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MedLine Citation:
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PMID: 20671427 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Methylation of tumor suppression genes (TSGs) is common in myeloid malignancies. However, application of this as a molecular marker for risk stratification in patients with AML is limited. DESIGN AND METHODS: To elucidate the impact of patterns of TSG methylation on outcome in cytogenetically normal patients, 106 samples from patients with having normal cytogenetic AML were evaluated for methylation of 12 genes by MSP. For sake of comparison, samples from patients with AML and abnormal cytogenetics (n = 63) were also evaluated. RESULTS: Methylation frequencies in the whole group (n = 169) were similar to previous reports for CDH1 (31%), ER (31%), FHIT (9%), p15 (INK4b) (44%), p73 (25%), and SOCS1 (75%). Methylation of CTNNA1 was observed in 10%, CEBP-α in16%, CEBP-δ in 2%, MLH1 in 24%, MGMT in 11% and DAPK in 2% of AML samples. We find that DNA methylation was more prevalent in patients with normal compared to karyotypically abnormal AML for most genes; CEBPα (20% vs 9%), CTNNA1 (14% vs 4%), and ER (41% vs 19%) (p < 0.05 for all comparisons). In contrast, p73 was more frequently methylated in patients with karyotypic abnormalities (17% vs 38%; p < 0.05), perhaps due to specific silencing of the pro-apoptotic promoter shifting p73 gene expression to the anti-apoptotic transcript. In AML patients with normal cytogenetics, TSG methylation was not associated with event free or overall survival in a multivariate analysis. Conclusions: In patients with AML, TSG methylation is more frequent in patients with normal karyotype than those with karyotypic abnormalities but does not confer independent prognostic information for patients with normal cytogenetics. |
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Authors:
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Elizabeth A Griffiths; Steven D Gore; Craig M Hooker; Helai P Mohammad; Michael A McDevitt; B Douglas Smith; Judith E Karp; James G Herman; Hetty E Carraway |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-01 |
Journal Detail:
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Title: Epigenetics : official journal of the DNA Methylation Society Volume: 5 ISSN: 1559-2308 ISO Abbreviation: Epigenetics Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2011-04-05 Completed Date: 2011-06-28 Revised Date: 2012-05-24 |
Medline Journal Info:
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Nlm Unique ID: 101265293 Medline TA: Epigenetics Country: United States |
Other Details:
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Languages: eng Pagination: 590-600 Citation Subset: IM |
Affiliation:
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The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Base Sequence CCAAT-Enhancer-Binding Proteins / genetics Case-Control Studies DNA Methylation DNA, Neoplasm / genetics DNA-Binding Proteins / genetics Epigenesis, Genetic* Genes, Tumor Suppressor HL-60 Cells Humans Karyotyping Leukemia, Myeloid, Acute / genetics* Middle Aged Nuclear Proteins / genetics Receptors, Estrogen / genetics Tumor Suppressor Proteins / genetics U937 Cells alpha Catenin / genetics fms-Like Tyrosine Kinase 3 / genetics |
| Grant Support | |
ID/Acronym/Agency:
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CA06793/CA/NCI NIH HHS; K24 CA111717/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CCAAT-Enhancer-Binding Proteins; 0/CEBPA protein, human; 0/CTNNA1 protein, human; 0/DNA, Neoplasm; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Receptors, Estrogen; 0/Tumor Suppressor Proteins; 0/alpha Catenin; 0/tumor suppressor protein p73; EC 2.7.10.1/FLT3 protein, human; EC 2.7.10.1/fms-Like Tyrosine Kinase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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