ABSTRACT
As many of the genetic mutations associated with malignancy in children appear to occur spontaneously, a double ‘hit’26 is a likely mechanism.
Knudson,26 in an attempt to understand the pathogenesis of neonatal retinoblastomas, extrapolated statistical data and proposed that retinoblastoma resulted from a combination of a prezygotic (germinal) mutation as well as postzygotic (somatic) event. This suggestion resulted in the so-called ‘two-hit’ theory, i.e. that retinoblastoma can be initiated by two events. Later on this was confirmed by Comings27 who suggested that both of these events could apply to mutations of the RB1 gene. It is now widely accepted that inherited or de novo chromosomal mutations or deletions may be may result in a susceptibility to cancer.
