Linked Life Data

17493032

Source:http://linkedlifedata.com/resource/pubmed/id/17493032

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-5-11
pubmed:abstractText
The aim of the present study was to elucidate genetic alterations that are critically involved in astrocytoma progression. We characterized 27 World Health Organization grade II fibrillary astrocytomas which later underwent recurrence or progression, paying specific attention to the CpG island methylation status of critical growth regulatory genes. p14(ARF) and O(6)-methylguanine-DNA methyltransferase (MGMT) hypermethylation represented frequent events (26% and 63%, respectively), which were mutually exclusive except in one case, with alternate or simultaneous methylation of these two genes occurring in 85% of our tumor series. Seventeen tumors (63%) contained TP53 mutations, which were closely related to the presence of MGMT methylation. Methylation of the p21(Waf1/Cip1), p27(Kip1) and p73 genes and homozygous deletion of the p16(INK4a), p15(INK4b) and p14(ARF) genes were not detected in any of the primary low-grade tumors. The presence of p14(ARF) methylation at first biopsy was associated with shorter patient survival, whereas the presence of MGMT methylation carried a better clinical outcome after salvage therapy. Examination of 20 cases whose histological data for recurrent tumors were available revealed that malignant progression occurred in all of the tumors with p14(ARF) methylation but less frequently (50%) in the lesions with MGMT methylation. On analysis of their respective recurrent tumors, five of six patients whose primary low-grade tumors carried p14(ARF) methylation exhibited homozygous co-deletions of the p14(ARF), p15(INK4b) and p16(INK4a) genes, which were restricted to glioblastoma as the most malignant end point. Our findings suggest that p14(ARF) hypermethylation and MGMT hypermethylation constitute distinct molecular pathways of astrocytoma progression, which could differ in biological behavior and clinical outcome.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1015-6305
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5-10
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Aberrant hypermethylation of p14ARF and O6-methylguanine-DNA methyltransferase genes in astrocytoma progression.
pubmed:affiliation
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan. takao@med.nihon-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't