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Hypothetical model. Tet2 depletion together with Nras mutation increase melanoma incidence and reduces the latency. In cooperation with Nras activation, Tet2 depletion would favor cell immortalization and facilitate melanoma emergence by (i) reducing cell-cycle inhibitor/tumor suppressor expression; (ii) allowing Akt activation, and (iii) reducing the hydroxymethylome plasticity, a bunch of phenomena that influence tumor homeostasis.
