Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.
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 http://www.iarc.fr/p53, 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.
Olivier
Magali
M
IARC, Lyon, Cedex 8, France.
Goldgar
David E
DE
Sodha
Nayanta
N
Ohgaki
Hiroko
H
Kleihues
Paul
P
Hainaut
Pierre
P
Eeles
Rosalind A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D030541:Databases, Genetic; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009369:Neoplasms / Q000235:genetics*; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics
D016159:Tumor Suppressor Protein p53