Driver mutations of cancer epigenomes Journal Article


Authors: Roy, D. M.; Walsh, L. A.; Chan, T. A.
Article Title: Driver mutations of cancer epigenomes
Abstract: Epigenetic alterations are associated with all aspects of cancer, from tumor initiation to cancer progression and metastasis. It is now well understood that both losses and gains of DNA methylation as well as altered chromatin organization contribute significantly to cancer-associated phenotypes. More recently, new sequencing technologies have allowed the identification of driver mutations in epigenetic regulators, providing a mechanistic link between the cancer epigenome and genetic alterations. Oncogenic activating mutations are now known to occur in a number of epigenetic modifiers (i.e. IDH1/2, EZH2, DNMT3A), pinpointing epigenetic pathways that are involved in tumorigenesis. Similarly, investigations into the role of inactivating mutations in chromatin modifiers (i.e. KDM6A, CREBBP/EP300, SMARCB1) implicate many of these genes as tumor suppressors. Intriguingly, a number of neoplasms are defined by a plethora of mutations in epigenetic regulators, including renal, bladder, and adenoid cystic carcinomas. Particularly striking is the discovery of frequent histone H3.3 mutations in pediatric glioma, a particularly aggressive neoplasm that has long remained poorly understood. Cancer epigenetics is a relatively new, promising frontier with much potential for improving cancer outcomes. Already, therapies such as 5-azacytidine and decitabine have proven that targeting epigenetic alterations in cancer can lead to tangible benefits. Understanding how genetic alterations give rise to the cancer epigenome will offer new possibilities for developing better prognostic and therapeutic strategies. © 2014 The Author(s).
Keywords: methylation; epigenetics; chromatin; mutations; cancer
Journal Title: Protein & Cell
Volume: 5
Issue: 4
ISSN: 1674-800X
Publisher: Higher Education Press  
Date Published: 2014-04-01
Start Page: 265
End Page: 296
Language: English
DOI: 10.1007/s13238-014-0031-6
PROVIDER: scopus
PMCID: PMC3978161
PUBMED: 24622842
DOI/URL:
Notes: Export Date: 1 May 2014 -- Source: Scopus
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MSK Authors
  1. Timothy Chan
    233 Chan
  2. Logan Alexander Walsh
    19 Walsh
  3. David Matthew Roy
    7 Roy