Genomic and Epigenomic Alterations in Cancer

Abstract

Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research.

Figure 1

Model depicting genomic and epigenetic events during cancer progression. Numerous genetic events, like gene amplifications, deletions, gene fusions, and mutations of oncogenes and tumor suppressor genes, are common in cancer. In addition, many histone modifiers also show aberrant regulation in cancer. These changes modulate gene expression during cancer progression. DNA methylation and demethylation are also common occurrence in cancer and lead to altered regulation of gene expression. Many of these genomic and epigenetic regulators are effective therapeutic targets in cancer. EGFR, epidermal growth factor receptor.