Complex replication error causes p53 mutation in a Li-Fraumeni family

Cancer Res. 1995 Aug 1;55(15):3237-41.


We demonstrated a germline p53 replication error in two generations of a Li-Fraumeni family affected with liposarcoma, adrenocortical carcinoma, and osteosarcoma. The trinucleotide repeat mutation changed 5'-AGT GTG GTG GTG-3' at codons 215-218 to 5'-AGT TGG TTG GTG GTG-3'. The predicted protein would be elongated by one amino acid (val216-->trp leu) without a change in charge. Detection of p53 in the adrenal tumor by immunostaining suggested that the mutant protein was expressed. Persistence of the mutation in the germline may suggest a defect in DNA repair in the family member first affected. This is the first report where germline transmission of replication-damaged p53 trinucleotide repeats is associated with the Li-Fraumeni syndrome.

Publication types

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

MeSH terms

  • Adrenal Cortex Neoplasms / genetics
  • Adrenal Cortex Neoplasms / metabolism
  • Adult
  • Base Sequence
  • Female
  • Genes, p53 / genetics*
  • Humans
  • Infant
  • Li-Fraumeni Syndrome / genetics*
  • Li-Fraumeni Syndrome / metabolism
  • Liposarcoma / genetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Osteosarcoma / genetics
  • Pedigree
  • Point Mutation / genetics*
  • Spermatic Cord
  • Tumor Suppressor Protein p53 / metabolism


  • Tumor Suppressor Protein p53