Abstract
SUCCESSIVE loss of function of both alleles of the retinoblastoma susceptibility gene (RB) on human chromosome 13 seems to be critical in the development of retinoblastoma1–3 and osteosarcoma4–6. In cases where the tumour is familial and susceptibility is inherited, a mutation in one of the alleles is carried in the germline7. We have recently shown that cytogenetically visible germline mutations are usually in the paternally derived gene8. Such a bias would not be expected for sporadic (non-familial) tumours, where both mutations occur in somatic tissue, but there has been some indication of a bias towards initial somatic mutation in the paternally derived gene on chromosome 11 in sporadic Wilms tumour9. We have now examined 13 sporadic osteosarcomas and find evidence which indicates that in 12 cases the initial mutation was in the paternal gene, suggesting the involvement of germinal imprinting in producing the differential susceptibility of the two genes to mutation.
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Toguchida, J., Ishizaki, K., Sasaki, M. et al. Preferential mutation of paternally derived RB gene as the initial event in sporadic osteosarcoma. Nature 338, 156–158 (1989). https://doi.org/10.1038/338156a0
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DOI: https://doi.org/10.1038/338156a0
