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The history of cancer epigenetics

Abstract

Since its discovery in 1983, the epigenetics of human cancer has been in the shadows of human cancer genetics. But this area has become increasingly visible with a growing understanding of specific epigenetic mechanisms and their role in cancer, including hypomethylation, hypermethylation, loss of imprinting and chromatin modification. This timeline traces the field from its conception to the present day. It also addresses the genetic basis of epigenetic changes — an emerging area that promises to unite cancer genetics and epigenetics, and might serve as a model for understanding the epigenetic basis of human disease more generally.

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Figure 1: Gatekeeper role for loss of imprinting of IGF2 in Wilms tumour.
Figure 2: Co-operative and self-reinforcing organization of the chromatin and DNA-modifying machinery responsible for gene silencing in normal and malignant cells.

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Acknowledgements

We thank E. Fearon, B. Vogelstein, R. Ohlsson and G. Klein for reading the manuscript. This work was supported by grants from the National Institutes of Health. We apologize in advance for any errors of omission or commission.

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DATABASES

Cancer.gov

acute lymphoblastic leukaemias

acute myelogenous leukaemia

cervical cancer

colon cancer

liver cancer

lung cancer

malignant rhabdoid tumour

pancreatic cancer

stomach cancer

uterine cancer

Wilms tumour

LocusLink

ALL1

ARHI

ATRX

BORIS

CAGE

calcitonin

CDKN1C

CTCF

DNMT1

DNMT3A

DNMT3B

EZH2

H19

HP1

HRAS

IGF2

LIT1

Lsh

MBD2

MDR1

MECP2

MLH1

Nf1

PEG3

PML

RARα

RARB2

RB

SLUG

SNF5

SUV39H1

Trp53

WT1

FURTHER INFORMATION

DNA Methylation Society

Imprinted Gene Catalogue

Imprinting

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Feinberg, A., Tycko, B. The history of cancer epigenetics. Nat Rev Cancer 4, 143–153 (2004). https://doi.org/10.1038/nrc1279

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