A previously undescribed mutation within the tetramerisation domain of TP53 in a family with Li-Fraumeni syndrome.
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.
Varley
J M
JM
CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, UK.
McGown
G
G
Thorncroft
M
M
Cochrane
S
S
Morrison
P
P
Woll
P
P
Kelsey
A M
AM
Mitchell
E L
EL
Boyle
J
J
Birch
J M
JM
Evans
D G
DG
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
D003062:Codon