CHAPTER 31
HETEROGENEITY OF DIFFERENTIAL EXPRESSION IN CANCER STUDIES: ALGORITHMS AND METHODS
31.1 INTRODUCTION
Cancer is an uncontrolled growth of abnormal cells evading apoptosis. It is a result of the failure of cell cycle control and apoptosis functions combined with an increased proliferation activity. Tumor formation and its progression to cancer causes major complex changes to the cells’ maps of genome, transcriptome, and pathway regulation [10, 34, 35]. For example, the genomes of cancer cells, compared with that of normal cells, contain extra copies of some chromosomal segments as a result of duplication, translocation, and deletion of some regions of the genome [34, 35]. Erratic genomic changes and cell cycle regulation lead to different pathways being activated and different sets of genes coming into play in defining the state of the cells. The changes depend on many factors related to the patient such as the genetic makeup and the stage of the tumor. For example, Grade3 tumors will have many more structural variations (amplifications and deletions) in their genomes and a stronger expression of proliferation associated genes compared with Grade1 tumors. Estrogen receptor (ER)+ tumor progression may be facilitated by different transcription factors and pathways compared with ER– tumors. Similarly, p53+ tumors grow potentially because of deregulation of the pathways downstream of p53, whereas the p53– tumors grow because of the deregulation ...
