title: A previously undescribed mutation within the tetramerisation domain of TP53 in a family with Li-Fraumeni syndrome.
abstract: We report details of a family with classic Li-Fraumeni syndrome in which there is a mutation in codon 344 of the tumour suppressor gene TP53. Codon 344 is a key residue within the tetramerisation domain, and the amino acid substitution of a proline for a leucine is predicted to have profound implications for tetramerisation and potentially DNA binding. This is the first report of a mutation at this residue in either sporadic tumours or in the germline and the first report of a germline mutation within the tetramerisation domain. The family does not appear to be remarkable in the spectrum of tumours, and there is loss of the wild-type allele in a leiomyosarcoma from the proband. A cell line has been established from the tumour of the proband and cytogenetic and molecular studies carried out, providing an extensive analysis in this family.
authors.affiliation: CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Varley
authors.forename: G
authors.initials: G
authors.lastname: McGown
authors.forename: M
authors.initials: M
authors.lastname: Thorncroft
authors.forename: S
authors.initials: S
authors.lastname: Cochrane
authors.forename: P
authors.initials: P
authors.lastname: Morrison
authors.forename: P
authors.initials: P
authors.lastname: Woll
authors.forename: A M
authors.initials: AM
authors.lastname: Kelsey
authors.forename: E L
authors.initials: EL
authors.lastname: Mitchell
authors.forename: J
authors.initials: J
authors.lastname: Boyle
authors.forename: J M
authors.initials: JM
authors.lastname: Birch
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007621:Karyotyping; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D003062:Codon