Chapter 2 - University of British Columbia

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