Introduction

The major known genomic alterations related to cancer include nucleotide substitution mutations, small insertions/deletions, copy number gains and losses, chromosomal rearrangements, and nucleic acids of foreign origin. Early genomics studies focused on examining only one type of genomic alteration at a time and achieved some success. For example, copy number variations have enabled the discovery of many oncogenes in ovarian cancer (Nanjundan et al., 2007), melanoma (Scott et al., 2009), and lung carcinoma (Bass et al., 2009). Similarly, directed sequencing technologies have found many genes related to specific types of cancer (Pao et al., 2004; Stephens et al., 2004; Mosse et al., 2008).

However, because different types of genomic alteration illuminate different aspects of the cancer genome, we can integrate several types of alteration derived from the same set of tumors to determine important genes involved in cancer initiation, development, and progression. There are two main advantages of such integration studies. The first is that integration can increase the precision, accuracy, and statistical power of identifying cancer-related genes compared with analyzing any single type of alteration. The reason for this is that cancer is thought to be primarily caused by random genetic alterations via different mechanisms. Although each type of alteration may be rare, the cumulative number of different alterations can indicate that a gene is important in a certain cancer. For example, The Cancer Genome Atlas (TCGA) glioblastoma project integrated targeted sequencing, copy number, and expression profiling of more than 400 tumor samples to define core pathways of deregulation in glioblastoma (The Cancer Genome Atlas Network, 2008) and discovered four molecular subtypes (Noushmehr et al., 2010; Verhaak et al., 2010).