Mutation and Cancer: Statistical Study of Retinoblastoma

TLDR

The authors aim to test the hypothesis that retinoblastoma is caused by two mutational events. The authors model retinoblastoma as a two‑step mutational process, with one germline mutation and a second somatic mutation producing an average of three tumors, and apply Poisson statistics to estimate equal germline and somatic mutation rates and to explain tumor multiplicity. The study proposes that retinoblastoma results from two mutational events and uses Poisson statistics to explain the observed patterns of unilateral, bilateral, and multiple tumors.

Abstract

Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye. This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.