Germ-line and somatic p53 gene mutations in multifocal osteogenic sarcoma. Multifocal osteogenic sarcoma patients without familial histories of increased tumor predisposition were examined for mutations in the highly conserved regions of the p53 gene. p53 point mutations were found in tumor DNA from each of the four patients we examined. A germ-line p53 mutation was detected in one of these patients, and a further rearrangement of the residual wild-type allele was detected in tumor tissue. p53 germ-line mutations can contribute to the enhanced predisposition to tumor development manifest in patients with multifocal osteosarcoma.