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: J M Varley, G McGown, M Thorncroft, S Cochrane, P Morrison, P Woll, A M Kelsey, E L Mitchell, J Boyle, J M Birch, D G Evans
• Journal: Oncogene (Oncogene) Vol. 12 Issue 11 Pg. 2437-42 (Jun 06 1996) ISSN: 0950-9232 [Print] England
• PMID: 8649785 (Publication Type: Journal Article)

Chemical References

• Codon

Topics

• Adult
• Alleles
• Base Sequence
• Codon (genetics)
• Female
• Genes, p53 (genetics)
• Genotype
• Humans
• Karyotyping
• Li-Fraumeni Syndrome (genetics)
• Male
• Molecular Sequence Data
• Pedigree
• Point Mutation (genetics)
• Sequence Analysis, DNA