Exclusion of a p53 germline mutation in a classic Li-Fraumeni syndrome family

Hum Genet. 1998 Jun;102(6):681-6. doi: 10.1007/s004390050761.


Li-Fraumeni syndrome (LFS) is characterized by a high risk of sarcomas, early onset of breast cancer, and a diversity of other cancers occurring as multiple primary tumors in multiple family members. In many families with LFS, germline mutations within the tumor-suppressor gene p53 have been identified. However, mutations in p53 have not been detected in approximately 30% of LFS families. To address the possibility either that p53 mutations were being missed or that another predisposing gene is altered in LFS, we used a variety of methods to accurately determine the p53 status in a large LFS kindred. A transcriptional activation assay on exons 4-10 of p53 excluded a mutation within the DNA-binding domain of p53. Single-stranded conformational-polymorphism analysis, using intronic primers and sequencing of all the coding exons and intron/exon junctions, also yielded no mutations. Finally, linkage analysis excluded potential mutations in the noncoding regions of p53. Our findings exclude the presence of a p53 germline mutation in a classic LFS family.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Female
  • Genes, p53*
  • Genetic Linkage
  • Germ-Line Mutation*
  • Humans
  • Li-Fraumeni Syndrome / genetics*
  • Male
  • Mutation
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Saccharomyces cerevisiae / genetics