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. Details 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=7x10(-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. The results 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.
Shonkwiler
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R
School of Mathematics, Georgia Institute of Technology, Atlanta, GA 30332, USA. shonkwiler@math.gatech.edu
Mistretta
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M
Varma
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V
D048708:Cell Growth Processes; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D009154:Mutation; D012175:Retinoblastoma / Q000235:genetics / Q000473:pathology*