Figure 1.

Interplay of key contributing factors to tumor heterogeneity. Both cell-intrinsic and cell-extrinsic factors contribute to tumor heterogeneity. Key cell-intrinsic factors include mutation, DNA-repair genes, epigenetic mechanisms, chromosome segregation and stability, as well as intracellular signaling. Non-genetic or phenotypic variations as a result of contributing cell-intrinsic factors are depicted by different cytoplasmic colors. Cell-extrinsic mechanisms affect and contribute to the unequal microenvironment, indirectly contributing to tumor heterogeneity. Multiple cell types and different inter- and intra-cell interactions within a tumor may exist (only representatives are shown here), hence selectively contributing to tumor heterogeneity.