title: The value of rapid functional assays of germline p53 status in LFS and LFL families.
abstract: We have tested two rapid assays of p53 function, namely the apoptotic assay and the FASAY as means of detecting germline p53 mutations in members of Li-Fraumeni and Li-Fraumeni-like families. Results of the functional assays have been compared with direct sequencing of all 11 exons of the p53 gene. The results show good agreement between the two functional assays and between them and sequencing. No false-positives or negatives were seen with either functional assay although the apoptotic assay gave one borderline result for an individual without a mutation. As an initial screen the apoptotic assay is not only rapid but inexpensive and very simple to perform. It would be expected to detect any germline defect that leads to loss of p53 function. The apoptotic assay could be ideal as a means of prescreening large numbers of samples and identifying those that require further investigation. The FASAY detects mutations in exons 4-10, is rapid and distinguishes between functionally important and silent mutations.
authors.affiliation: Richard Dimbleby Department of Cancer Research, Guy's Kings and St Thomas' Medical School, St Thomas' Hospital, London, UK.
authors.forename: R S
authors.initials: RS
authors.lastname: Camplejohn
authors.forename: N
authors.initials: N
authors.lastname: Sodha
authors.forename: R
authors.initials: R
authors.lastname: Gilchrist
authors.forename: M E
authors.initials: ME
authors.lastname: Lomax
authors.forename: P M
authors.initials: PM
authors.lastname: Duddy
authors.forename: C
authors.initials: C
authors.lastname: Miner
authors.forename: P
authors.initials: P
authors.lastname: Alarcon-Gonzalez
authors.forename: D M
authors.initials: DM
authors.lastname: Barnes
authors.forename: R A
authors.initials: RA
authors.lastname: Eeles
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D001681:Biological Assay / Q000379:methods; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D015203:Reproducibility of Results; D018570:Risk Assessment