Chapter 2 - University of British Columbia
Chapter 2 - University of British Columbia
Chapter 2 - University of British Columbia
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generated over 500,000 data points per sample, representing a 100-fold increase in information<br />
obtained from each experiment [99]. Hence, the base s<strong>of</strong>tware architecture used in SIGMA 2<br />
was already capable <strong>of</strong> handling large amounts <strong>of</strong> data.<br />
Aim 2: Demonstration <strong>of</strong> an integrative approach using model systems<br />
<strong>Chapter</strong> 3 discusses the demonstration <strong>of</strong> an integrative, multi-dimensional approach on tumor<br />
cell line model systems. Using a set <strong>of</strong> breast cancer cell lines, I examine the gene dosage,<br />
allelic composition, DNA methylation, and gene expression pr<strong>of</strong>iles in an integrative manner to<br />
delineate which genes and pathways would be missed or less significant if such an approach<br />
was not used. This demonstrative study was needed to show the key advantages and benefits<br />
<strong>of</strong> an integrative approach. While cell lines are artificial systems and may have acquired<br />
alterations that are beneficial to grow in vitro, it is important that a sample source was used<br />
where material limitations did not exist. For each <strong>of</strong> the genetic or epigenetic pr<strong>of</strong>iling studies,<br />
sufficient amounts <strong>of</strong> DNA and RNA are needed and when more assays are done in a given<br />
sample, more material is required. Moreover, when whole tumor samples are microdissected to<br />
ensure high tumor cell purity, this inherently will reduce the amount <strong>of</strong> usable sample material.<br />
As such, it is important that the quantitative and qualitative benefits <strong>of</strong> utilizing an integrative<br />
approach are sufficient to warrant using clinical samples. At the time this study was initiated,<br />
SNP array and array CGH pr<strong>of</strong>iles were available for breast cancer cell lines and thus, only<br />
generation <strong>of</strong> DNA methylation and gene expression pr<strong>of</strong>iles were needed to complete this set.<br />
Given the purpose <strong>of</strong> this study was to demonstrate the effectiveness <strong>of</strong> the integrative<br />
approach, while data from lung cancer cell lines would have been most optimal, the source <strong>of</strong><br />
data has limited relevance to the purpose <strong>of</strong> this aim.<br />
Aim 3: Characterization <strong>of</strong> DNA level alterations in lung adenocarcinoma<br />
A number <strong>of</strong> studies have been done to identify gene dosage alterations in lung cancer and in<br />
lung adenocarcinoma specifically. These studies were done on a number <strong>of</strong> different array<br />
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