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

Autor: Olli Tynninen, Hannu Haapasalo, Tea Blom, Kristiina Nordfors, Miikka Korja, Nina N. Nupponen, Valtteri Häyry, Kirmo Wartiovaara, Annariikka Roselli
Rok vydání: 2009
Předmět:
Zdroj: Journal of Neuro-Oncology. 97:217-224
ISSN: 1573-7373
0167-594X
DOI: 10.1007/s11060-009-0014-2
Popis: 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). We investigated protein expression and gene copy numbers of KIT, PDGFRA, and VEGFR2 in 41 MB 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, and VEGFR2 amplifications were all present in 4% of MBs/PNETs, and KIT amplification was associated with concurrent PDGFRA and VEGFR2 amplifications (Por= 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.
Databáze: OpenAIRE
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