Characterization of germline TP53 splicing mutations and their genetic and functional analysis

Oncogene. 2001 May 10;20(21):2647-54. doi: 10.1038/sj.onc.1204369.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Alternative Splicing / physiology*
  • Cell Line
  • Fibroblasts / physiology
  • Genes, p53 / genetics*
  • Germ-Line Mutation / genetics
  • Germ-Line Mutation / physiology*
  • Humans
  • Immunohistochemistry
  • Introns
  • Li-Fraumeni Syndrome / genetics
  • Loss of Heterozygosity
  • Lymphocytes / physiology
  • Neoplasms / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Tumor Suppressor Protein p53