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Abstract
Colorectal cancer (CRC) results from a stepwise accumulation of genetic and epigenetic alterations that transform the normal colonic epithelium into cancer. DNA methylation represents one of the most studied epigenetic marks in CRC, and three common epigenotypes have been identified characterized by high, intermediate and low methylation profiles, respectively. Combining DNA methylation data with gene mutations and cytogenetic alterations occurring in CRC is nowadays allowing the characterization of different CRC subtypes, but the crosstalk between DNA methylation and other epigenetic mechanisms, such as histone tail modifications and the deregulated expression of non-coding RNAs is not yet clearly defined. Epigenetic biomarkers are increasingly recognized as promising diagnostic and prognostic tools in CRC, and the potential of therapeutic applications aimed at targeting the epigenome is under investigation.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Colorectal cancer (CRC) is a heterogeneous disease evolving through a stepwise accumulation of genetic and epigenetic alterations.
Large-scale DNA methylation studies revealed three common epigenotypes characterized by high, intermediate and low methylation profiles, respectively.
Combining methylation epigenotypes with gene mutations and cytogenetic alterations occurring in CRC is allowing the characterization of different CRC subtypes.
DNA methylation biomarkers are increasingly recognized as valuable diagnostic and prognostic tools.
Post-translational modifications of the histone tails occur in the average CRC genome, the most studied being acetylation and methylation.
The diagnostic and prognostic potential of histone tail modifications in CRC is limited if compared with other epigenetic marks.
Altered expression levels of several noncoding RNAs have been documented in all the phases of CRC development and progression.
The analysis of tumor-derived miRNAs in human body fluids is a promising diagnostic tool for CRC, and the potential of therapeutic applications aimed at selectively targeting certain miRNAs is under investigation.