Every single cell of an organism contains largely the same DNA. Therefore, non-genetic mechanisms are required to enable the generation of specialized, phenotypically distinct cells as found in different organs. Such lineage commitment is mediated by epigenetic mechanisms, which determine a heritable change in gene expression without affecting the DNA sequence. Intense epigenetic research over the last 15 years has provided substantial insights into the complex molecular machinery that regulates histone and DNA modifications to determine transcriptional output, adding significantly to our understanding of fundamental biological processes including embryonic development, homeostasis, and disease pathogenesis.
Whereas the genomic landscape of cancer has been well documented by large-scale genomic analysis, the epigenetic landscape is emerging. Alterations in regulators of the epigenome affect multiple target genes simultaneously and allow rewiring of complex signaling circuits. Such epigenetic reprogramming is implicated in the early stages of tumorigenesis, when pre-malignant lesions progress into invasive malignancies and is closely linked to aggressive phenotypes of advanced disease states like metastasis and therapy resistance.
Did you know that large-scale cancer genomic analysis identified epigenetic regulators among the most mutated genes in cancer?
Did you know that of around 125 commonly mutated genes in cancer around 40 are epigenetic regulators?