Novel p53 splice site mutations in three families with Li-Fraumeni syndrome

Oncogene. 2000 Aug 31;19(37):4230-5. doi: 10.1038/sj.onc.1203758.


Germline mutations in the p53 tumor suppressor gene predispose to a variety of cancers in families with Li-Fraumeni syndrome. Most germline p53 mutations observed to date cause amino acid substitutions in the protein's central sequence-specific DNA binding domain. Outside this conserved core region, however, we found novel alterations in sequences that regulate precursor mRNA splicing in three Li-Fraumeni syndrome families. Two splice site mutations affected the consensus sequence at the splice donor sites of introns 1 and 9, and produced unstable variant transcripts in normal cells. A third mutation at the splice acceptor site of intron 9 generated splicing at a cryptic acceptor site in intron 9. These splice site alterations emphasize the need to examine both noncoding and untranslated regions of the p53 gene for germline mutations in Li-Fraumeni syndrome families. Oncogene (2000) 19, 4230 - 4235

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cells, Cultured / metabolism
  • Codon / genetics
  • Consensus Sequence
  • DNA Mutational Analysis
  • Female
  • Genes, p53*
  • Genotype
  • Humans
  • Introns / genetics
  • Keratinocytes / metabolism
  • Li-Fraumeni Syndrome / genetics*
  • Male
  • Molecular Sequence Data
  • Pedigree
  • RNA Splicing / genetics*
  • RNA, Messenger / genetics


  • Codon
  • RNA, Messenger