Chapter 2 - University of British Columbia
Chapter 2 - University of British Columbia
Chapter 2 - University of British Columbia
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Finally, using publicly microarray datasets with patient survival information [250-252], Kaplan-<br />
Meier analysis was performed on each <strong>of</strong> these datasets based on SIRPA expression levels.<br />
The association was deemed significant if the gene had a p-value ≤ 0.05 based on a Mantel-<br />
Cox (or log ranks) test. Two <strong>of</strong> the five datasets showed a statistically significant association<br />
between SIRPA expression levels and overall patient survival with an additional two datasets<br />
close to significance with p values ≤ 0.18 (Figure 5.9).<br />
5.5 Tracking clonal expansion in spatial dimensions<br />
Delineating the clonal relationship between multiple tumors in the same patient is relevant not<br />
only to clinical management <strong>of</strong> disease but also to the understanding <strong>of</strong> metastasis. Multiple<br />
tumors in the same patient may not necessarily share an identical genomic pr<strong>of</strong>ile. The<br />
similarities and differences in genomic landscape between tumors are quantifiable and therefore<br />
can be used for delineating relatedness. Whole genome comparison based on array CGH<br />
pr<strong>of</strong>iles is a new tool for distinguishing metastatic from primary synchronous carcinomas. A<br />
multitude <strong>of</strong> genomic features, for example the boundaries <strong>of</strong> segmental deletions, are used to<br />
delineate the presence and the sequence <strong>of</strong> events in clonal evolution [253-261].<br />
Furthermore, signature genetic alterations can be used to track clonality in a cell population,<br />
putting genetic events in the context <strong>of</strong> tumor tissue architecture. By assessing the appearance<br />
<strong>of</strong> pre-selected markers in individual nuclei on a tissue section by FISH, the clustering and the<br />
expansion <strong>of</strong> clonally related cells can be delineated by analyzing the marker patterns <strong>of</strong><br />
neighboring cells (Figure 5.10).<br />
5.6 Evaluating the biological significance <strong>of</strong> integrative genomics<br />
findings<br />
The utilization <strong>of</strong> an integrative genomic, epigenomic and transcriptomic approach will<br />
undoubtedly improve our ability to identify gene disruptions and their effects on gene<br />
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