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dc.contributor.authorHowley, R
dc.contributor.authorKinsella, P
dc.contributor.authorBuckley, P G
dc.contributor.authorAlcock, L
dc.contributor.authorJansen, M
dc.contributor.authorHeffernan, J
dc.contributor.authorStallings, R L
dc.contributor.authorBrett, F M
dc.contributor.authorAmberger-Murphy, V
dc.contributor.authorFarrell, M A
dc.date.accessioned2012-10-24T11:50:42Z
dc.date.available2012-10-24T11:50:42Z
dc.date.issued2012-10-15
dc.identifier.citationComparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ. 2012, 318 (17):2245-56 Exp. Cell Res.en_GB
dc.identifier.issn1090-2422
dc.identifier.pmid22705586
dc.identifier.doi10.1016/j.yexcr.2012.06.007
dc.identifier.urihttp://hdl.handle.net/10147/250041
dc.description.abstractDeveloping targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRβ were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.
dc.language.isoenen
dc.rightsArchived with thanks to Experimental cell researchen_GB
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshBrain Neoplasms
dc.subject.meshComparative Genomic Hybridization
dc.subject.meshFemale
dc.subject.meshGenomics
dc.subject.meshGlioma
dc.subject.meshHumans
dc.subject.meshImmunoenzyme Techniques
dc.subject.meshIn Situ Hybridization, Fluorescence
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Grading
dc.subject.meshPTEN Phosphohydrolase
dc.subject.meshProteomics
dc.subject.meshReceptor, Epidermal Growth Factor
dc.subject.meshReceptor, Platelet-Derived Growth Factor alpha
dc.subject.meshReceptor, Platelet-Derived Growth Factor beta
dc.subject.meshSignal Transduction
dc.subject.meshTumor Cells, Cultured
dc.subject.meshTumor Markers, Biological
dc.subject.meshYoung Adult
dc.titleComparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Neuropathology, Beaumont Hospital, Dublin 9, Ireland. rhowley@rcsi.ieen_GB
dc.identifier.journalExperimental cell researchen_GB
dc.description.provinceLeinsteren
html.description.abstractDeveloping targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRβ were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.


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