FIGURE 2 | The epigenetic progenitor model of cancer.

From the following article:

The epigenetic progenitor origin of human cancer

Andrew P. Feinberg, Rolf Ohlsson & Steven Henikoff

Nature Reviews Genetics 7, 21-33 (January 2006)

doi:10.1038/nrg1748

The epigenetic progenitor origin of human cancer

According to this model, cancer arises in three steps. First is an epigenetic alteration of stem/progenitor cells within a given tissue, which is mediated by aberrant regulation of tumour-progenitor genes (TPG). This alteration can be due to events within the stem cells themselves, the influence of the stromal compartment, or environmental damage or injury. Second is a gatekeeper mutation (GKM) (tumour-suppressor gene (TSG) in solid tumours, and rearrangement of oncogene (ONC) in leukaemia and lymphoma). Although these GKMs are themselves monoclonal, the expanded or altered progenitor compartment increases the risk of cancer when such a mutation occurs and the frequency of subsequent primary tumours (shown as separately arising tumours). Third is genetic and epigenetic instability, which leads to increased tumour evolution. Note that many of the properties of advanced tumours (invasion, metastasis and drug resistance) are inherent properties of the progenitor cells that give rise to the primary tumour and do not require other mutations (highlighting the importance of epigenetic factors in tumour progression).

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