DICER1 and DICER1-related tumor predisposition: The highly penetrant and severe phenotypes described in patients with germline or mosaic RNase III domain mutations5 6 may be explained by the likelihood of a second somatic mutation stochastically occurring in any part of DICER1 being greater than the reverse succession normally seen in DICER1 syndrome, in combination with tissue-specific neomorphic effects of the specific heterozygous RNase III domain mutations.11