Chapter 2 - University of British Columbia
Chapter 2 - University of British Columbia
Chapter 2 - University of British Columbia
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quantitative PCR experiments as well as microarray experiments where relative quantifications<br />
are typically used. To address this, using SAGE, where quantification <strong>of</strong> expression is absolute,<br />
genes whose expression was constant across both malignant and non-malignant samples were<br />
identified [103]. Those genes demonstrated better constancy than some genes which are<br />
typically used as controls for gene expression analysis.<br />
1.12.4 Integration <strong>of</strong> gene dosage and gene expression in lung cancer<br />
The first level <strong>of</strong> genomic integration that needed to be accomplished was the integration <strong>of</strong><br />
gene dosage and gene expression. In one study using cancer cell lines, hot spots <strong>of</strong> DNA<br />
amplification were identified throughout the genome. When specifically examining lung cancer<br />
cell lines and subsequently coupling this with gene expression data, it was found that 50% <strong>of</strong><br />
genes in these frequently amplified regions show correlation between gene dosage and gene<br />
expression [52]. Moreover, it was also observed that different components <strong>of</strong> the EGFR<br />
signaling pathway were amplified in different cell lines illustrating that for a given pathway, one<br />
can underestimate the frequency <strong>of</strong> pathway disruption when only well known genes in the<br />
pathway are assessed.<br />
In a second study involving clinical lung tumors, a genomic region which was preferentially<br />
amplified in squamous cell carcinomas as compared to adenocarcinomas was identified.<br />
Further integration with gene expression data allowed for the identification <strong>of</strong> the target gene,<br />
BRF2, in this amplified region [104]. Moreover, gene dosage and protein expression level<br />
assessment <strong>of</strong> CIS samples for BRF2 showed that amplification and overexpression were<br />
present, suggesting that this event is occurring at an early stage <strong>of</strong> tumorigenesis.<br />
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