title: Epigenetic drivers and genetic passengers on the road to cancer.
abstract: Cancer is traditionally viewed as a primarily genetic disorder, however it is now becoming accepted that cancer is also a consequence of abnormal epigenetic events. Genetic changes and aneuploidy are associated with alterations in DNA sequence, and they are a hallmark of the malignant process. Epigenetic alterations are universally present in human cancer and result in heritable changes in gene expression and chromatin structure over many cell generations without changes in DNA sequence, leading to functional consequences equivalent to those induced by genetic alterations. Importantly, intriguing evidence emerged suggesting that epigenetic changes may precede and provoke genetic changes. In this scenario, epigenetic events are primary events while genetic changes (such as mutations) may simply be a consequence of disrupted epigenetic states. This fact may explain why many genetic screens proved to be limited with regard to cancer causality and pathogenesis. Aberrant epigenetic events affect multiple genes and cellular pathways in a non-random fashion and this can predispose to induction and accumulation of genetic changes in the course of tumour initiation and progression. These considerations are critical for a better understanding of tumourigenesis and molecular events underlying the acquisition of drug resistance, as well as development of novel strategies for cancer therapy and prevention.
authors.affiliation: International Agency for Research on Cancer, 150 Cours Albert Thomas, Rhone-Alpes, 69008 Lyon, France.
authors.forename: Carla
authors.initials: C
authors.lastname: Sawan
authors.forename: Thomas
authors.initials: T
authors.lastname: Vaissière
authors.forename: Rabih
authors.initials: R
authors.lastname: Murr
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
mesh_terms: D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones