Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

6.3 Copy Number Aberrations Results
Figure 6.7: The image summarises the results of the CGH arrays performed on
cell lines G144, G166 and G179. Dots indicate log2 ratios for array CGH probes
along the genome, comparing each GNS line to normal female DNA. The coloured
segments indicate gain (red) and loss (green) calls, with colour intensity proportional
to mean log2 ratio over the segment. The X chromosome was called as lost in G144
and G179 because these two cell lines are from male patients; sex-linked genes were
excluded from downstream analyses of aberration calls. The red segments above the
grey line at zero indicate gains and red segments below it indicate losses over the
entire genome.
On a global level, we found a correlation between aberrations and expression
levels, but this trend was modest (Fig 6.8a). Among the 459 autosomal genes
that we found to be up-regulated in GNS relative to NS lines by Tag-seq,
there was a clear enrichment of gains (p = 0.002 with Fisher’s exact test) and
depletion of losses (p = 0.002) compared to all autosomal genes expressed in
the GNS or NS lines. Down-regulated genes showed an opposite, but weaker,
trend (Table 6.3, Fig 6.8b). We also observed that many of the 29 genes that
were found to distinguish GNS lines from NS lines by qRT-PCR had associ-
ated aberration calls that suggested their expression levels may be dictated
by a loss or a gain in their copy numbers (Fig 6.8c). Overall, these results
Table 6.3: Significance of the correlation found between CNAs and expression levels
measured with Fisher’s exact test (p-value).
Gains Losses
Up-regulated 0.002163 0.002286
Down-regulated 0.06997 0.4257
suggest that copy number changes are a significant cause of the observed gene
expression changes. However, other factors may be more important, because
only a minority of up-regulated genes (21%) showed evidence of gains. Thus,
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