Figure 2. From Ribosomopathy to Cancer: A Model of Selective Mutation.

In healthy cells, ribosome biogenesis is tightly regulated and exists in a homeostatic balance that is determined by the overall demand for protein synthesis. Ribosomopathies develop when mutations in genes involved in ribosome biogenesis lead to hypoproliferation resulting from p53-dependent or -independent cell cycle arrest and apoptosis. Clonal selection for cells harboring mutations in tumor-suppressor genes that enables bypass of normal surveillance mechanisms can result in a population with decreased capacity for high fidelity ribosome biogenesis. Continued enrichment of this functionally deficient population gives rise to additional mutations that enable cellular transformation to cancer. This model was adapted from Sulima et al. [62].