Amplification and overexpression of KIT, PDGFRA, and VEGFR2 in medulloblastomas and primitive neuroectodermal tumors.
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 <or= 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.
Blom
Tea
T
Molecular Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, University of Helsinki, Finland. Tea.Blom@helsinki.fi
Roselli
Annariikka
A
Häyry
Valtteri
V
Tynninen
Olli
O
Wartiovaara
Kirmo
K
Korja
Miikka
M
Nordfors
Kristiina
K
Haapasalo
Hannu
H
Nupponen
Nina N
NN
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics; D019089:Stem Cell Factor / Q000096:biosynthesis* / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis* / Q000235:genetics
D019089:Stem Cell Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2