Epigenetic marks in normal and cancer cells DNA methylation and histone modifications have crucial roles in the control of gene activity and nuclear

| An altered pattern of epigenetic modifications is central to many common human diseases, including cancer. Many studies have explored the mosaic patterns of DNA methylation and histone modification in cancer cells on a gene-by-gene basis; among their results has been the seminal finding of transcriptional silencing of tumour-suppressor genes by CpG-island-promoter hypermethylation. However, recent technological advances are now allowing cancer epigenetics to be studied genome-wide — an approach that has already begun to provide both biological insight and new avenues for translational research. It is time to ‘upgrade’ cancer epigenetics research and put together an ambitious plan to tackle the many unanswered questions in this field using epigenomics approaches. R E V I E W S 286 | APRIL 2007 | VOLUME 8 www.nature.com/reviews/genetics © 2007 Nature Publishing Group E3 E1 E2 E1 E2 E1 E2 E3 E1 E2 • DNA hypomethylation • ‘Open’ or ‘relaxed’ chromatin conformation Cancer cell • CpG-island hypermethylation • ‘Closed’ chromatin conformation Normal cell • Tumour-suppressor gene with promoter CpG island • ‘Open’ chromatin conformation • Locus with methylated 5′-regulatory region, e.g. germline-specific gene • Repetitive sequences, e.g. transposable element • Entry into cell cycle • Avoidance of apoptosis • Defects in DNA repair • Angiogenesis • Loss of cell adhesion • Loss of imprinting and overgrowth • Inappropiate cell-type expression • Genome fragility • Activation of endoparasitic sequences Tumorigenesis Unmethylated CpG Methylated CpG