Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.
Cancer Res
; 63(20): 6643-50, 2003 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-14583457
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Genes p53
/
Síndrome de Li-Fraumeni
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Mutação em Linhagem Germinativa
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Bases de Dados Genéticas
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article