Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

7.2 Glioblastoma Expression Signatures Results
regulation and the presentation of extracellular peptides can potentially be
completed for recognition from T helper cells. As for MHC class I-mediated
immunogenicity, our study identifies two important players as strongly up-
regulated in GNS cell lines, HLA-A and TAP1. The protein encoded by TAP1
is an ATP binding cassette transporter involved in the pumping of degraded
cytosolic peptides across the ER into the vesicles where MHC class I receptors
such as HLA-A assemble. TAP1 has been show to interact with TAPBP and
HLA-A [386]. Similarly to the expression observed for MHC class II molecules,
the over-expression of these MHC class I molecules seems to suggest that part
of the endogenous pathway might also be activated in immunosurveillance
response mechanisms in GNS cell lines. We find an overall transcriptional
up-regulation of MHC class II molecules and a smaller subset of MHC class I
molecules, suggestive of the absence of transcriptionally active compensatory
mechanisms. However, it is impossible with the available data to determine
what happens at the post-transcriptional and post-translational level because
this up-regulation should be checked against protein expression data.
7.2 Glioblastoma Expression Signatures
Analysis of microarray gene expression data for hundreds of high-grade glioma
samples and a smaller number of xenografts have shown that most tumours
can be classified into a small number of subtypes correlated with survival and
response to therapy [148,390,511]. The largest such study to date identified
four glioblastoma subtypes, each characterised by a distinct gene expression
signature encompassing 210 genes [511]. The subtypes were named "proneu-
ral", "neural", "classical" and "mesenchymal" based on which genes were up-
regulated in their respective expression signatures. To investigate whether
these subtype signatures could be captured by our Tag-seq data, Tag-seq ex-
pression data for three primary glioblastoma tumours, 11 xenografts and two
normal brain samples was analysed, which had been produced with the same
Tag-seq protocol used on our GNS and NS cell lines by Parsons et al [383].
The correlations were highly significant (p < 0.01) for all tumour and xenograft
samples and both normal brain samples (Fig 7.3), confirming that Tag-seq cap-
tures the subtype expression signatures previously observed in large microarray
datasets. Specifically, of the tumour and xenograft samples, three were classi-
fied as proneural, seven as classical and three as mesenchymal. However, both
normal brain samples and none of the glioblastoma samples, were classified as
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