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Article: Molecular analysis of microdissected de novo glioblastomas and paired astrocytic tumors

TitleMolecular analysis of microdissected de novo glioblastomas and paired astrocytic tumors
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date1999
PublisherAmerican Association of Neuropathologists, Inc. The Journal's web site is located at http://www.aanp-jnen.com
Citation
Journal of Neuropathology and Experimental Neurology, 1999, v. 58 n. 2, p. 120-128 How to Cite?
AbstractGlioblastoma 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.
Persistent Identifierhttp://hdl.handle.net/10722/91240
ISSN
2015 Impact Factor: 3.432
2015 SCImago Journal Rankings: 2.136
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheng, Yen_HK
dc.contributor.authorNg, H-Ken_HK
dc.contributor.authorDing, Men_HK
dc.contributor.authorZhang, S-Fen_HK
dc.contributor.authorPang, JC-Sen_HK
dc.contributor.authorLo, K-Wen_HK
dc.date.accessioned2010-09-17T10:15:28Z-
dc.date.available2010-09-17T10:15:28Z-
dc.date.issued1999en_HK
dc.identifier.citationJournal of Neuropathology and Experimental Neurology, 1999, v. 58 n. 2, p. 120-128en_HK
dc.identifier.issn0022-3069en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91240-
dc.description.abstractGlioblastoma 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.en_HK
dc.languageengen_HK
dc.publisherAmerican Association of Neuropathologists, Inc. The Journal's web site is located at http://www.aanp-jnen.comen_HK
dc.relation.ispartofJournal of Neuropathology and Experimental Neurologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.titleMolecular analysis of microdissected de novo glioblastomas and paired astrocytic tumorsen_HK
dc.typeArticleen_HK
dc.identifier.emailCheng, Y:yuecheng@hku.hken_HK
dc.identifier.authorityCheng, Y=rp1320en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid10029095-
dc.identifier.scopuseid_2-s2.0-0032986688en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032986688&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume58en_HK
dc.identifier.issue2en_HK
dc.identifier.spage120en_HK
dc.identifier.epage128en_HK
dc.identifier.isiWOS:000078903300002-

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