title: Tumor protein 53 mutations and inherited cancer: beyond Li-Fraumeni syndrome.
abstract: OBJECTIVE
  Germline TP53 (tumor protein 53) mutations are the molecular basis of a complex cancer predisposition syndrome, the Li-Fraumeni syndrome. The present review discusses the diversity of tumor patterns in TP53 mutation carriers, focusing on molecular factors that may explain familial and individual differences, such as genotype/phenotype correlations, genetic modifiers and genetic anticipation.
  
  
  RESULTS
  Initially identified 20 years ago, germline TP53 mutations appear to be associated with an extremely diverse range of cancers. Although no other gene has been found in Li-Fraumeni syndrome, recent results show that the functional effects of particular mutations, polymorphisms in TP53 or in regulators such as MDM2 (murine double minute 2), variations in DNA copy number and variations in telomere length, have a strong impact on individual risk and on tumor patterns. Furthermore, recent studies in large cohorts suggest that TP53 germline mutations may occur in up to 1: 5000 individuals.
  
  
  CONCLUSIONS
  Germline TP53 mutations may be responsible for a large fraction (15-20%) of all inherited cancers. Although mutations are detectable by sequencing, counseling and follow-up remain problematic due to the wide variations in disease presentation. Elucidating the molecular mechanisms underlying the predisposition caused by TP53 deficiency may help to develop better, evidence-based and personalized clinical protocols.
authors: International Agency for Research on Cancer, Group of Molecular Carcinogenesis, Lyon, France.
authors: Edenir I
authors: EI
authors: Palmero
authors: Maria Iw
authors: MI
authors: Achatz
authors: Patricia
authors: P
authors: Ashton-Prolla
authors: Magali
authors: M
authors: Olivier
authors: Pierre
authors: P
authors: Hainaut
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53