Epigenetics and cancer

Since Laennec, parallels had been noted between cancer and development (epigenesis) with the idea that cancer might consist of the inappropriate acquisition of properties of cells at different developmental stages. Indeed, some of the earliest described cancers were teratomas (from the Greek words "teras" (monster) and "onkoma" (swelling) coined by Virchow in 1863), which can have anatomically identifiable features, such as fingers, teeth and hair. Although the molecular pathways may be similar in cancer and development, the "rules" of their use are very different. Indeed, unlike embryogenesis where the same genome gives rise to many different epigenomes, in cancer cells both genomes and epigenomes change. In fact, tumors are evolutionary entities, with both genetic and epigenetic changes occurring, that can enable rapid selection. Recent new insights thanks to the sequencing of human cancer genomes, as well as genetic manipulation in model organisms, have reconciled these two views and led to the exciting discovery that many of the mutations in cancer actually lie in genes encoding proteins and non-coding RNAs involved in epigenetic processes. Thus mutations in epigenetic modifiers, such as DNA methyltransferases or demethylases, chromatin enzymes and remodelers can promote oncogenesis, by altering epigenetic marks that impact on gene expression and genome stability. Thanks to functional studies in mouse models, our understanding of specific epigenetic mechanisms and their roles in cancer has increased dramatically. Furthermore, it is now realized that epigenetic plasticity likely plays a key role in generating cellular heterogeneity within tumors, and enabling the dialogue with the stroma that can facilitate cell proliferation, angiogenesis as well as invasion. Today, we understand that the interplay between genetic and epigenetic changes in cancer is implicated at every step of tumor progression, from the incipient neoplasm, through to metastasis.