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A decade of exploring the cancer epigenome — biological and translational implications

Abstract

The past decade has highlighted the central role of epigenetic processes in cancer causation, progression and treatment. Next-generation sequencing is providing a window for visualizing the human epigenome and how it is altered in cancer. This view provides many surprises, including linking epigenetic abnormalities to mutations in genes that control DNA methylation, the packaging and the function of DNA in chromatin, and metabolism. Epigenetic alterations are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis. The enzymatic processes that control the epigenome present new opportunities for deriving therapeutic strategies designed to reverse transcriptional abnormalities that are inherent to the cancer epigenome.

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Figure 1: Model of the overall structure of the epigenome in normal human cells.
Figure 2: The cancer epigenome and relevant gene mutations.
Figure 3: Modes of abnormal gene silencing in cancer.

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Acknowledgements

The authors thank all of their present and former colleagues in their laboratories for their provision of data and discussions. They also thank all of their colleagues in the field who have contributed the data discussed in this article and apologize to all those whose work has not been included because of space constraints. They are grateful to K. Bender and S. Olivo for help in preparation of the manuscript. Portions of work cited from the authors' laboratories were supported by grants from the US National Cancer Institute (NCI) and National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH), and by The Cancer Genome Atlas Project (TCGA) funded by the National Genome and National Cancer Institutes. They are also grateful for the support of the Entertainment Industry Foundation (EIF) and the American Association for Cancer Research (AACR), via the Stand up to Cancer (SU2C) project, for work aimed at bringing epigenetic therapy to the forefront of cancer management.

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Correspondence to Stephen B. Baylin or Peter A. Jones.

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S.B.B. consults for MDX Health Inc., Constellation, BioNumerik and SuperGen. P.A.J. is a consultant for Lilly.

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Baylin, S., Jones, P. A decade of exploring the cancer epigenome — biological and translational implications. Nat Rev Cancer 11, 726–734 (2011). https://doi.org/10.1038/nrc3130

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