title: A TP53 mutation detected in cells established from an osteosarcoma, but not in the retinoblastoma of a patient with bilateral retinoblastoma and multiple primary osteosarcomas.
abstract: A patient with bilateral retinoblastoma and subsequent multiple primary osteosarcomas has been described previously. Osteosarcoma cell lines established from this patient were shown to express a shortened RB1 mRNA transcript and no detectable normal Rb protein. We now show that the osteosarcoma cell lines have lost one TP53 allele and contain a mutation in exon 8 codon 286 [GAA to AAA (Glu to Lys)] in the remaining allele. Consequently, the osteosarcoma cell lines have no normal Rb protein and no normal p53 protein. Neither constitutional DNA nor DNA extracted from a retinoblastoma of the left eye of the patient contained the TP53 mutation, suggesting that the TP53 mutation in the osteosarcoma cells may represent a tumor-promoting mutation, which confers a selective growth advantage. If both RB1 and TP53 are involved in the initiation of osteosarcoma, the mechanisms for development of the retinoblastoma and osteosarcoma tumors are different.
authors.affiliation: Department of Genetics, Norwegian Radium Hospital, Oslo.
authors.forename: E
authors.initials: E
authors.lastname: Hovig
authors.forename: A
authors.initials: A
authors.lastname: Andreassen
authors.forename: B M
authors.initials: BM
authors.lastname: Fangan
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen
mesh_terms: D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics; D004586:Electrophoresis / Q000379:methods; D005134:Eye Neoplasms / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012175:Retinoblastoma / Q000235:genetics*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D016159:Tumor Suppressor Protein p53