Recent advances in basic and clinical science have driven epigenetics to the forefront of cancer research. Together with genetic changes, the disruption of epigenetic mechanisms is now established as a hallmark of cancer in humans. Colorectal cancer, long a classic model for the genetic basis of cancer, is now providing researchers with the opportunity to view epigenetic events in the context of neoplasia in humans. Knowledge of the heritable changes in gene expression that result from epigenetic events is of increasing relevance to clinical practice, particularly in terms of diagnostic and prognostic molecular markers, as well as novel therapeutic targets.

BACKGROUND

Colorectal cancer, for many years a prototypic model for the genetic basis of cancer, is now increasingly cited as an exemplar of the role of epigenetic changes in tumorigenesis. In part, this is because colorectal neoplasia provides a wide range of accessible lesions, from aberrant crypt foci to carcinoma. It also serves as a poster child for epigenetic change because of the possible role that DNA methylation has in the initiation and progression of this disease. For both these reasons, it provides an excellent opportunity to understand how epigenetics and genetics collude to produce malignancy.

This review will provide a broad overview of common epigenetic processes as they occur in the normal cell and in the cancer cell, and will highlight recent findings in the epigenetics of colorectal neoplasia. It will briefly discuss the clinical implications of epigenetic changes, in terms of both the identification of disease predisposition and the therapeutic opportunities that a better understanding of these changes may provide. The term epigenetics, while variously defined,¹ will be used in this review to describe those heritable changes in gene function that do not entail a change in DNA sequence.² Table 1 shows the key historical milestones in …