Sustaining cancer through addictive ectopic gene activation

Abstract

Systematic genetic and epigenetic alterations occurring in almost all cancer cells result in the ectopic expression of a variety of tissue-specific potent regulatory factors. This review sheds light on a new aspect of cancer based on the integration of the 'out of context' activity of tissue-restricted genes into the biology of cancer cells. A systematic screen for the ectopic activation of tissue-restricted genes in a variety of cancers has revealed that many normally silent genes are expressed in tumours of all origins. This aberrant gene activation not only could be used as a source of biomarkers, but also, in several cases, reveals clear oncogenic mechanisms associated with the corresponding ectopically expressed factors. The characteristic of all cancer cells, which systematically reprogram tissue-specific gene expression and activate silent genes, can be exploited to develop new anticancer strategies aiming at the detection of malignant states, the prediction of their evolution and drug sensitivity and the discovery of new therapeutic approaches.