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Cancer is a disease of the genome. Each cancer is the result of a unique combination of germline and somatic mutations that could include nucleotide substitutions, insertions and deletions, chromosomal rearrangements and copy number changes in protein-coding or regulatory components of genes (1). In addition, cancer genomes may exhibit changes in DNA methylation and chromatin structure that can have a substantial impact on gene expression. A comprehensive catalog of all types of variants in a cancer opens new and unrivaled opportunities for understanding the mechanism of cancer onset and progression, predicting the response to therapeutics, and providing new biomarkers for diagnosis and prognosis.
The impact of next-generation DNA sequencing technology
The last 10 years have transformed our understanding of the cancer genome through a remarkable revolution in genome sequencing technology (2,3). In 2001, the Human Genome Project delivered the first draft of the human genome at a cost of $3B (4). By 2008, the cost had dropped to $2M (5). In 2012, a human genome can be sequenced for less than $5000. The dramatic increase in throughput and the drop in the cost of sequencing offers an unprecedented opportunity to comprehensively understand a cancer by determining all genomic variations, evaluating the impact of these DNA variations on the transcriptome (by RNA sequencing) and delineating the changes in the interactions of the genome with histones, enzymes, and transcription factors by sequencing DNA fragments associated with specific proteins (6).