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

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    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
    Issue Date
    2012-10-15
    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
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    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
    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
    ISSN
    1090-2422
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.yexcr.2012.06.007
    Scopus Count
    Collections
    Beaumont Hospital

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