Somatic and germinal mutations of tumor-suppressor genes in the development of cancer.

It is generally thought that the germinal mutation of tumor-suppressor genes predisposes the affected children to the development of certain types of hereditary tumors while the somatic mutation of the same genes links to the development of non-hereditary tumors. Retinoblastoma susceptibility gene (RB gene) is a prototype of such genes. We studied the parental origin of new mutation of the RB gene in the sporadic hereditary and non-hereditary retinoblastoma and osteosarcoma. The results showed a preferential involvement of parental genome in the new germinal as well as initial somatic mutations. The male-directed mutagenesis even in the somatic cells has been implicated as a reflection of germinal origin of mutation, even for non-hereditary tumors as a manifestation of mutational mosaicism associated with delayed mutation. The importance of the new mutations occurring as mosaics should be emphasized in the evaluation of cancer risks from parental exposures to radiation and chemicals.