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Journal of Neuro-Oncology

, Volume 97, Issue 2, pp 217–224 | Cite as

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
Laboratory Investigation - Human/Animal Tissue

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). 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 (P ≤ 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.

Keywords

Amplification KIT PDGFRA VEGFR2 Medulloblastoma 

Notes

Acknowledgments

This work has been supported by the Academy of Finland, Instrumentarium Foundation, K. Albin Johansson Foundation, Finnish Cultural Foundation, The Paulo Foundation, Orion and Farmos Research Foundation, Jalmari and Rauha Ahokas Foundation, Maud Kuistila Foundation, the Biomedicum Helsinki Foundation, the Cancer Society of Finland, and the Medical Research Fund of Tampere University Hospital. We greatly thank Gynel Arifdshan for skilful technical assistance and James Thompson for language editing.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Tea Blom
    • 1
  • Annariikka Roselli
    • 1
  • Valtteri Häyry
    • 2
  • Olli Tynninen
    • 3
  • Kirmo Wartiovaara
    • 2
  • Miikka Korja
    • 4
  • Kristiina Nordfors
    • 5
  • Hannu Haapasalo
    • 5
  • Nina N. Nupponen
    • 1
  1. 1.Molecular Cancer Biology Program, Biomedicum HelsinkiUniversity of HelsinkiUniversity of HelsinkiFinland
  2. 2.Medical Biochemistry and Developmental Biology, Institute of BiomedicineUniversity of HelsinkiUniversity of HelsinkiFinland
  3. 3.Department of PathologyHelsinki University Central HospitalUniversity of HelsinkiFinland
  4. 4.Department of Medical Biochemistry and Molecular BiologyUniversity of TurkuTurkuFinland
  5. 5.Department of PathologyTampere University HospitalTampereFinland

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