Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype

Cancer Res. 2003 Oct 15;63(20):6643-50.


A database has been created to collect information on families carrying a germ-line mutation in the TP53 gene and on families affected with Li-Fraumeni syndromes [Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL)]. Data from the published literature have been included. The database is available online at, as part of the IARC TP53 Database. The analysis of the 265 families/individuals that have been included thus far has revealed several new findings. In classical LFS families with a germ-line TP53 mutation (83 families), the mean age of onset of breast cancer was significantly lower than in LFS families (16 families) without a TP53 mutation (34.6 versus 42.5 years; P = 0.0035). In individuals with a TP53 mutation, a correlation between the genotype and phenotype was found. Brain tumors were associated with missense TP53 mutations located in the DNA-binding loop that contact the minor groove of DNA (P = 0.01), whereas adrenal gland carcinomas were associated with missense mutations located in the loops opposing the protein-DNA contact surface (P = 0.003). Finally, mutations likely to result in a null phenotype (absence of the protein or loss of function) were associated with earlier onset brain tumors (P = 0.004). These observations have clinical implications for genetic testing and tumor surveillance in LFS/LFL families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child, Preschool
  • Databases, Genetic*
  • Female
  • Genes, p53 / genetics*
  • Germ-Line Mutation*
  • Humans
  • Li-Fraumeni Syndrome / genetics*
  • Male
  • Middle Aged
  • Models, Molecular
  • Neoplasms / genetics*
  • Sex Factors
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics


  • Tumor Suppressor Protein p53