Linked Life Data

18172295

Source:http://linkedlifedata.com/resource/pubmed/id/18172295

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-1-3
pubmed:abstractText
To identify epigenetically silenced cancer-related genes and to determine molecular effects of 5-aza-2'-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) in multiple myeloma (MM), we analyzed global changes in gene expression profiles of three MM cell lines by microarray analysis. We identified up-regulation of several genes whose epigenetic silencing in MM is well known. However, much more importantly, we identified a large number of epigenetically inactivated cancer-related genes that are involved in various physiologic processes and whose epigenetic regulation in MM was unknown thus far. In addition, drug treatment of MM cell lines resulted in down-regulation of several MM proliferation-associated factors (i.e., MAF, CCND1/2, MYC, FGFR3, MMSET). Ten Aza-dC and/or TSA up-regulated genes (CPEB1, CD9, GJA1, BCL7c, GADD45G, AKAP12, TFPI2, CCNA1, SPARC, and BNIP3) were selected for methylation analysis in six MM cell lines, 24 samples from patients with monoclonal gammopathy of undetermined significance (MGUS), and 111 samples from patients with MM. Methylation frequencies of these genes ranged between 0% and 17% in MGUS samples and between 5% and 50% in MM samples. Interestingly, methylation of SPARC and BNIP3 was statistically significantly associated with a poor overall survival of MM patients (P = 0.003 and P = 0.017, respectively). Moreover, SPARC methylation was associated with loss of SPARC protein expression by immunostaining in a subset of MM patients. In conclusion, we identified new targets for aberrant methylation in monoclonal gammopathies, and our results suggest that DNA methyltransferase and histone deacetylase inhibition might play an important role in the future treatment of patients with MM.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
44-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18172295-Antimetabolites, Antineoplastic, pubmed-meshheading:18172295-Azacitidine, pubmed-meshheading:18172295-DNA, Neoplasm, pubmed-meshheading:18172295-DNA Methylation, pubmed-meshheading:18172295-DNA Modification Methylases, pubmed-meshheading:18172295-Enzyme Inhibitors, pubmed-meshheading:18172295-Epigenesis, Genetic, pubmed-meshheading:18172295-Gene Expression Profiling, pubmed-meshheading:18172295-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18172295-Genes, Neoplasm, pubmed-meshheading:18172295-Genome, Human, pubmed-meshheading:18172295-Histone Deacetylase Inhibitors, pubmed-meshheading:18172295-Humans, pubmed-meshheading:18172295-Hydroxamic Acids, pubmed-meshheading:18172295-Multiple Myeloma, pubmed-meshheading:18172295-Transcription, Genetic, pubmed-meshheading:18172295-Tumor Cells, Cultured
pubmed:year
2008
pubmed:articleTitle
Genome-wide transcriptional response to 5-aza-2'-deoxycytidine and trichostatin a in multiple myeloma cells.
pubmed:affiliation
Division of Oncology, Department of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't