A previously undescribed mutation within the tetramerisation domain of TP53 in a family with Li-Fraumeni syndrome
Varley, J.M.; McGown, G.; Thorncroft, M.; Cochrane, S.; Morrison, P.; Woll, P.; Kelsey, A.M.; Mitchell, E.L.; Boyle, J.; Birch, J.M.; Evans, D.G.
Oncogene 12(11): 2437-2442
1996
ISSN/ISBN: 0950-9232 PMID: 8649785 Document Number: 465641
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.