title: Characterization of germline TP53 splicing mutations and their genetic and functional analysis.
abstract: Germline TP53 splicing mutations have been described infrequently (>2%) in the literature, however in a series of 40 patients and families identified by our group in which there are germline TP53 mutations, seven affect splicing (18%). The low figure reported in the literature might reflect the method of mutation detection, which in many studies does not include all splice junctions. These data indicate that a significant proportion of TP53 germline mutations are currently unrecognized. We have carried out detailed studies of the effects of the different mutations on splicing, and see distinct variations in the effects of the same mutation in different patients. Furthermore we have identified the usage of a non-consensus splice donor site in four families with an intron 4 splice donor mutation.
authors: CRC Cancer Genetics Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, UK.
authors: J M
authors: JM
authors: Varley
authors: C
authors: C
authors: Attwooll
authors: G
authors: G
authors: White
authors: G
authors: G
authors: McGown
authors: M
authors: M
authors: Thorncroft
authors: A M
authors: AM
authors: Kelsey
authors: M
authors: M
authors: Greaves
authors: J
authors: J
authors: Boyle
authors: J M
authors: JM
authors: Birch
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005347:Fibroblasts / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns; D016864:Li-Fraumeni Syndrome / Q000235:genetics; D019656:Loss of Heterozygosity; D008214:Lymphocytes / Q000502:physiology; D009369:Neoplasms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
chemical_list: D016159:Tumor Suppressor Protein p53