The genetics of childhood cancer

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Abstract
Retinoblastoma should not be considered as the exceptional childhood cancer that shows dominant inheritance, but rather as the typical childhood cancer that embraces a prezygotic and postzygotic subgroup. Postzygotic cases are conceived as involving mutation as a first step too, but with the mutation in somatic rather than germinal cells. In both prezygotic and postzygotic cases a second event, possibly mutational, occurs before the cancer is initiated. The embryonal cancers are all visualized as genetic disease, and their frequencies limited by gene mutability. This mutability can be increased by environmental agents. Prezygotic cases may develop other primary tumors in other tissues. They may also have affected family members, the probability of affected offspring approaching 50%. A diagnostic test to identify prezygotic cases among those with a single primary tumor and a negative family history is sorely needed.

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