title: Heterogeneity in Li-Fraumeni families: p53 mutation analysis and immunohistochemical staining.
abstract: We have screened two families for constitutional TP53 mutations, one family with Li-Fraumeni syndrome and the other with features of this syndrome. We report a germline mutation in exon 7 of the TP53 gene in the family with "Li-Fraumeni-like" syndrome. The mutation occurred at codon 245 and causes a Gly-Ser amino acid change. It was inherited by both affected and unaffected subjects. Malignant tumours from all members of this family showed strong positive nuclear immunohistochemical staining with antibodies CM-1 and DO1, directed against TP53. In contrast, no constitutional TP53 mutations were found in a "classic" Li-Fraumeni family. In this family positive staining was seen in both malignant and normal tissues. These results support previous findings that variants of the Li-Fraumeni syndrome exist since not all LFS families carry TP53 germline mutations. Secondly, immunohistochemical positivity is not synonymous with an underlying mutation and is therefore inadequate as an exclusive diagnostic marker.
authors.affiliation: Imperial Cancer Research Fund Human Genetic Resources, Clare Hall Laboratories, South Mimms, Potters Bar, UK.
authors.forename: C
authors.initials: C
authors.lastname: MacGeoch
authors.forename: G
authors.initials: G
authors.lastname: Turner
authors.forename: L G
authors.initials: LG
authors.lastname: Bobrow
authors.forename: D M
authors.initials: DM
authors.lastname: Barnes
authors.forename: D T
authors.initials: DT
authors.lastname: Bishop
authors.forename: N K
authors.initials: NK
authors.lastname: Spurr
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000276:immunology; D008297:Male; D010375:Pedigree; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000276:immunology
chemical_list: D016159:Tumor Suppressor Protein p53