Chapter 2 - University of British Columbia

List of Figures
Figure 1.1. Multiple mechanisms of alteration leading to same downstream consequences ..... 17
Figure 2.1. Main structural components of SIGMA2. .................................................................. 34
Figure 2.2. Data structure hierarchy. .......................................................................................... 35
Figure 2.3. Algorithm for integrating between different array platforms ...................................... 36
Figure 2.4. SIGMA2 interface. .................................................................................................... 37
Figure 2.5. Consensus calling and heterogeneous array analysis. ............................................ 38
Figure 2.6. Integrative genetic analysis of HCC2218 .................................................................. 40
Figure 2.7. Two-group two dimensional comparison of 37 NSCLC and 16 SCLC cancer cell
lines. ............................................................................................................................................ 41
Figure 2.8. Multi-dimensional perspective of chromosome 17 of the HCC2218 breast cancer cell
line. ............................................................................................................................................. 42
Figure 3.1. Genomic profiles of breast cancer cell lines. ............................................................ 65
Figure 3.2. Quantitative and qualitative benefits of integrative analyses. ................................... 66
Figure 3.3. Determination and application of a disruption frequency threshold. ......................... 68
Figure 3.4. Impact of multi-dimensional analysis on low frequency events. ............................... 69
Figure 3.5. Pathway analysis of the 1162 genes identified by multi-dimensional analysis. ........ 70
Figure 3.6. Complex deregulation of the Neuregulin/ERBB2 signaling pathway. ....................... 71
Figure 3.7. Deregulation of PTEN occurs differently between samples. ..................................... 72
Figure 3.8. Multiple concerted disruption (MCD) analysis and its application to triple negative
breast cancer. ............................................................................................................................. 73
Figure 4.1. Detection of UPD using allele specific copy number. ............................................... 88
Figure 4.2. Comparison of frequent regions of gain, loss and UPD in the lung adenocarcinoma
genome ....................................................................................................................................... 90
Figure 4.3. Venn diagram illustrating the amount of the genome covered by gain, loss, and UPD
.................................................................................................................................................... 92
Figure 4.4. Genomic profile of an individual lung adenocarcinoma sample ............................... 93
Figure 4.5. Examination of UPD events at the KRAS and RB1 loci ............................................ 95
Figure 4.6. Relationship of homozygous mutation at oncogenes and genomic alteration .......... 96
Figure 4.7. Identification of E2F3 in a focal region of UPD ......................................................... 97
Figure 5.1. Advances in cancer genomic landscape post Y2K. ................................................ 129
Figure 5.2. SNP array analysis to identify areas of altered copy number and allelic composition
in a clinical lung cancer specimen. ........................................................................................... 130
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