All cancers have genes that are permanently silenced by DNA methylation. Yeshayahu Schlesinger, Howard Cedar (The Hebrew University, Israel), and colleagues, and Martin Widschwendter (UCL, London, UK), Peter Laird (USC, Los Angeles, CA), and colleagues inspect these irreversibly silenced genes. In normal tissues, they find, these genes carry transient repression signals, which are inappropriately made permanent in cancer.
Large parts of the genome get methylated and thus permanently silenced in the early embryo, but genes associated with CpG islands are spared. Some are instead transiently repressed by a complex called polycomb. This prevents inappropriate expression during development, but allows repression to be reversed when needed.
Irreversible silencing by DNA methylation does occur at many CpG island genes during cancer progression. Schlesinger et al. now show that >60% of genes that are methylated in colon cancer are marked by polycomb in normal tissues. In an accompanying...
