Linked Life Data

18616639

Source:http://linkedlifedata.com/resource/pubmed/id/18616639

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-3-17
pubmed:abstractText
Methylation of CpG islands in gene promoters can lead to gene silencing. Together with deletion or mutation, it may cause a loss of function of tumor suppressor genes. RASSF1A (3p21.3), NORE1A (1q32.1) and BLU (3p21.3) have been shown to be downregulated by methylation in cancer, and PTEN (10q23.3) and MGMT (10q26.1) are located in areas commonly deleted in astrocytomas. MGMT methylation predicts a better response and a longer overall survival in patients with glioblastomas treated with temozolomide. We analyzed 53 astrocytoma samples and 10 high-grade glioma cell lines. Gene expression was assessed by RT-PCR. Bisulfite sequencing, MSP and a melting curve analysis-based real-time PCR were performed to detect promoter methylation. Treatments with 5'-aza-2'-deoxicitidine were applied to restore gene expression in cell lines. Ninety-two percent of tumor samples were methylated for RASSF1A, 30%-57% for BLU and 47% for MGMT, suggesting promoter methylation of these genes to be a common event in glioma tumorigenesis. Only 4% of the tumors revealed a methylated promoter for NORE1A. No association between methylation and loss of expression could be established for PTEN. We identified de novo DNMTs overexpression in a subset of tumors which may explain the methylation phenotype of individual gliomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/DNA (Cytosine-5-)-Methyltransferase, http://linkedlifedata.com/resource/pubmed/chemical/DNA Modification Methylases, http://linkedlifedata.com/resource/pubmed/chemical/DNA Repair Enzymes, http://linkedlifedata.com/resource/pubmed/chemical/MGMT protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Monomeric GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase, http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/RASSF1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/RASSF5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/ZMYND10 protein, human
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1750-3639
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
279-92
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
RASSF1A, BLU, NORE1A, PTEN and MGMT expression and promoter methylation in gliomas and glioma cell lines and evidence of deregulated expression of de novo DNMTs.
pubmed:affiliation
Brain Tumor Biology Unit, University of Navarra, Irunlarrea 1, Pamplona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't