title: Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.
abstract: Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.
authors.affiliation: Division of Molecular Genetics, Massachusetts General Hospital Cancer Center, Charlestown 02129.
authors.forename: D
authors.initials: D
authors.lastname: Malkin
authors.forename: F P
authors.initials: FP
authors.lastname: Li
authors.forename: L C
authors.initials: LC
authors.lastname: Strong
authors.forename: J F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: C E
authors.initials: CE
authors.lastname: Nelson
authors.forename: D H
authors.initials: DH
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Kassel
authors.forename: M A
authors.initials: MA
authors.lastname: Gryka
authors.forename: F Z
authors.initials: FZ
authors.lastname: Bischoff
authors.forename: M A
authors.initials: MA
authors.lastname: Tainsky
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D003062:Codon; D004247:DNA / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific; D016158:Genes, p53; D005820:Genetic Testing; D005854:Germ Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid; D012509:Sarcoma / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53; D004247:DNA; D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases