Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-3-4
pubmed:abstractText
Glioblastoma multiforme (GBM) often displays morphological heterogeneity in that low-grade (LG) area with well-differentiated cells are commonly found adjacent to high-grade (HG) area with poorly-differentiated cells. This heterogeneity may cause difficulty in obtaining representative tumor samples. Nevertheless, the genetic composition of these cells has only been occasionally examined. In the present study, we examined 29 de novo glioblastomas in which distinct LG and HG areas of sufficient volumes could be identified. These areas were microdissected from paraffin-embedded tissues and analyzed for genetic alterations: p53 mutations and immunohistochemistry; allelic losses at 17p13.1, 9p21, and 10q23-25; and amplification of the epidermal growth factor receptor (EGFR) gene and immunohistochemistry. We also examined 14 paired astrocytic tumors, in which a primary Grade II astrocytoma progressed over a period of time to a Grade III or Grade IV tumor. Our findings showed that the LG areas of the de novo glioblastomas exhibited numerous genetic aberrations, the proportion of which was increased in the HG areas. Genetic abnormalities seen in the LG areas were conserved in the HG areas suggesting that these morphologically different cellular subsets were derived from a common transformed clone. Also, the LG areas were genetically different from Grade II astrocytomas of the paired tumor group, in spite of their morphological similarity. In particular, the LG areas had more deletions on 10q23-25 (75% vs 20%, p = 0.04), but fewer p53 mutations (24% vs 71%, p = 0.003) and less p53 protein labeling (45% vs 79%, p = 0.04). These differences suggest that LG and HG areas in de novo glioblastoma are genetically closer to each other compared with paired low- and high-grade tumors that have progressed over time. Moreover, only a small proportion (17%) of our de novo glioblastomas exhibited EGFR amplification while a high proportion (62%) showed either p53 mutations or allelic loss of 17p13.1. We speculate that some de novo GBMs with copious LG areas may constitute a separate group with rapid progression from Grade II astrocytomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
120-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10029095-Adult, pubmed-meshheading:10029095-Aged, pubmed-meshheading:10029095-Alleles, pubmed-meshheading:10029095-Antibodies, Monoclonal, pubmed-meshheading:10029095-Astrocytes, pubmed-meshheading:10029095-Brain Neoplasms, pubmed-meshheading:10029095-Chromosome Mapping, pubmed-meshheading:10029095-DNA, Neoplasm, pubmed-meshheading:10029095-DNA, Satellite, pubmed-meshheading:10029095-Dissection, pubmed-meshheading:10029095-Female, pubmed-meshheading:10029095-Fixatives, pubmed-meshheading:10029095-Formaldehyde, pubmed-meshheading:10029095-Gene Deletion, pubmed-meshheading:10029095-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10029095-Genetic Heterogeneity, pubmed-meshheading:10029095-Glioblastoma, pubmed-meshheading:10029095-Heterozygote, pubmed-meshheading:10029095-Humans, pubmed-meshheading:10029095-Male, pubmed-meshheading:10029095-Middle Aged, pubmed-meshheading:10029095-Mutation, pubmed-meshheading:10029095-Paraffin Embedding, pubmed-meshheading:10029095-Polymerase Chain Reaction, pubmed-meshheading:10029095-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:10029095-Receptor, Epidermal Growth Factor, pubmed-meshheading:10029095-Tumor Suppressor Protein p53
pubmed:year
1999
pubmed:articleTitle
Molecular analysis of microdissected de novo glioblastomas and paired astrocytic tumors.
pubmed:affiliation
Department of Anatomical & Cellular Pathology, the Chinese University of Hong Kong, Shatin.
pubmed:publicationType
Journal Article