title: Two germ-line mutations affecting the same nucleotide at codon 257 of p53 gene, a rare site for mutations.
abstract: Codon 257 of the p53 gene is an extremely rare target for somatic mutations (accounting for only two of 1600 published mutations). We report here two constitutional mutations both affecting the second nucleotide of codon 257. A thymine to adenine transversion resulting in an amino acid change from leucine to glutamine was found in one proband who developed multiple independent malignant tumors (osteosarcoma, phyllodes tumor, soft-tissue sarcoma). Her mother died of early-onset breast cancer. In the other case, a deletion resulting in a frameshift in the C-terminal coding region of p53 was found in a woman who was diagnosed with breast cancer at age 34. This woman belongs to a family with features of Li-Fraumeni syndrome. In both cases, the p53 mutations identified in the proband was found in other members of the family. Codon 257, even if rarely mutated in somatic cells, may thus be an important target for germ-line mutations.
authors.affiliation: Laboratoire d'Oncologie Moléculaire--CJF INSERM 9302, Centre Léon Bérard, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Mazoyer
authors.forename: P
authors.initials: P
authors.lastname: Lalle
authors.forename: C
authors.initials: C
authors.lastname: Moyret-Lalle
authors.forename: C
authors.initials: C
authors.lastname: Marçais
authors.forename: S
authors.initials: S
authors.lastname: Schraub
authors.forename: D
authors.initials: D
authors.lastname: Frappaz
authors.forename: H
authors.initials: H
authors.lastname: Sobol
authors.forename: M
authors.initials: M
authors.lastname: Ozturk
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D003062:Codon; D005260:Female; D016368:Frameshift Mutation; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D008969:Molecular Sequence Data; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics; D010375:Pedigree; D003557:Phyllodes Tumor / Q000235:genetics; D012509:Sarcoma / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000235:genetics
chemical_list: D003062:Codon