Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.

2.50
Hdl Handle:
http://hdl.handle.net/10147/250041
Title:
Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.
Authors:
Howley, R; Kinsella, P; Buckley, P G; Alcock, L; Jansen, M; Heffernan, J; Stallings, R L; Brett, F M; Amberger-Murphy, V; Farrell, M A
Affiliation:
Department of Neuropathology, Beaumont Hospital, Dublin 9, Ireland. rhowley@rcsi.ie
Citation:
Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ. 2012, 318 (17):2245-56 Exp. Cell Res.
Journal:
Experimental cell research
Issue Date:
15-Oct-2012
URI:
http://hdl.handle.net/10147/250041
DOI:
10.1016/j.yexcr.2012.06.007
PubMed ID:
22705586
Abstract:
Developing 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.
Item Type:
Article
Language:
en
MeSH:
Adult; Aged; Brain Neoplasms; Comparative Genomic Hybridization; Female; Genomics; Glioma; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Male; Middle Aged; Neoplasm Grading; PTEN Phosphohydrolase; Proteomics; Receptor, Epidermal Growth Factor; Receptor, Platelet-Derived Growth Factor alpha; Receptor, Platelet-Derived Growth Factor beta; Signal Transduction; Tumor Cells, Cultured; Tumor Markers, Biological; Young Adult
ISSN:
1090-2422

Full metadata record

DC FieldValue Language
dc.contributor.authorHowley, Ren_GB
dc.contributor.authorKinsella, Pen_GB
dc.contributor.authorBuckley, P Gen_GB
dc.contributor.authorAlcock, Len_GB
dc.contributor.authorJansen, Men_GB
dc.contributor.authorHeffernan, Jen_GB
dc.contributor.authorStallings, R Len_GB
dc.contributor.authorBrett, F Men_GB
dc.contributor.authorAmberger-Murphy, Ven_GB
dc.contributor.authorFarrell, M Aen_GB
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.en_GB
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

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