A growth and division model for retinoblastoma

A stochastic growth and division model for studying a two hit cancer is developed and applied to retinoblastoma. Retinoblastoma occurs if both genes coding for a tumor suppressor protein on homologous chromosomes become defective. Germinal cases occur when a patient or carrier, born with one defective gene, suffers a second insult to any progeny retinal cell. Somatic cases are far less likely as two hits to the same cell during development are required. s of the disease, germinal or somatic, unilateral or bilateral, in combination with case data allow for the estimation of the two parameters of the model: mutation rate, estimated at p = 7 × 10−7 per chromosome per cell division, and carrier frequency, estimated at f = 40 per million. The model indicates that carriers of the disease arise from similar mutations to germ cells; in particular, heridary transmission can occur for only a generation or two before dying out. sults show that a stochastic simulation of a multi-hit cancer is feasible and may predict tumor growth dynamics. A simulation run will have to consist of a few million cells in order to observe even a small number of mutations. And several dozens such runs will have to be simulated.