Book of abstract 2008

A glioblastoma-specific kinase expression profile
Philip C. De Witt Hamer and Cornelis J.F. Van Noorden
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Specific kinase inhibition induces clinically relevant responses in kinase driven human
cancers. The best kinases to target by small molecular inhibitors are often unknown. We
address the issue of the best treatment targets for glioblastoma in relation to other human
malignancies, such as lung, breast, colon, renal and prostate cancer, based on differential
gene expression compared to normal tissues. For this purpose, we retrieved array expression
data from 34 publicly available datasets of a wide variety of tumor types, including two
glioma datasets, and extracted the differential gene expression data for the kinase gene
family consisting of 518 protein kinases and 33 lipid kinases. Kinases were ordered based
on levels and frequencies of overexpression in the patient population. The upper 5% of
percentile fold changes was considered to be substantial overexpression and expression in
more than 20% of the patient population was considered as frequent overexpression. In
both glioma datasets, 9 kinases appeared to be substantially and frequently overexpressed,
MAPK7, DDR2, EGFR, WEE1, TTK, AURKA, CDC2, MELK and BUB1. Two of these
9 selected kinases, EGFR and AURKA, have been described previously as overexpressed
in human glioblastoma samples, confirming the plausibility of the glioblastoma-specific
kinase profile. Moreover, selective inhibition of EGFR has shown response in a subgroup of
glioma patients. We also confirmed overexpression of the 9 kinase genes with quantitative
RT-PCR in samples of glioblastoma and glioma cell lines compared to normal brain from
our institution’s Brain Tumor Bank. Four of the 9 kinases were exclusively overexpressed
in glioblastoma, MAPK7, DDR2, EGFR and WEE1, whereas MELK, TTK, AURKA,
CDC2 and BUB1 were frequently overexpressed in various cancer types. The four
glioblastoma specific overexpressed kinases are putative treatment targets because these
were overexpressed early in gliomagenesis and therefore, may be causal.
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