Amplification and overexpression of KIT, PDGFRA, and VEGFR2 in medulloblastomas and primitive neuroectodermal tumors

Tea Blom*, Annariikka Roselli, Valtteri Häyry, Olli Tynninen, Kirmo Wartiovaara, Miikka Korja, Kristiina Nordfors, Hannu Haapasalo, Nina N. Nupponen

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    35 Citations (Scopus)

    Abstract

    Medulloblastomas (MB) and primitive neuroectodermal tumors (PNET) are the most common malignant brain tumors in children. These two tumor types are histologically similar, but have different genetic backgrounds and clinical outcomes. Other brain tumors, such as gliomas, frequently have coamplification and overexpression of receptor tyrosine kinases KIT, platelet-derived growth factor receptor alpha (PDGFRA), and vascular endothelial growth factor receptor 2 (VEGFR2).Weinvestigated protein expression and gene copy numbers ofKIT,PDGFRA, andVEGFR2 in 41MB and 11 PNET samples by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).KIT and PDGFRA expression was detected in both MBs and PNETs, whereas VEGFR2 expression was weak in these tumors. KIT, PDGFRA, andVEGFR2 amplificationswere all present in 4% of MBs/PNETs, and KIT amplification was associated with concurrent PDGFRA and VEGFR2 amplifications (P B 0.001). Most strikingly, increased gene copy number of PDGFRA was associated with poor overall survival (P = 0.027). We suggest that coamplification of PDGFRA or VEGFR2 with KIT may be clinically useful novel molecular markers in MBs and PNETs.

    Original languageEnglish
    Pages (from-to)217-224
    Number of pages8
    JournalJournal of Neuro-Oncology
    Volume97
    Issue number2
    DOIs
    Publication statusPublished - Apr 2010

    Keywords

    • Amplification
    • KIT
    • Medulloblastoma
    • PDGFRA
    • VEGFR2

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