An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma.
Proc Natl Acad Sci U S A
; 98(16): 9330-5, 2001 Jul 31.
Article
em En
| MEDLINE
| ID: mdl-11481490
ABSTRACT
The incidence of pediatric adrenal cortical carcinoma (ACC) in southern Brazil is 10-15 times higher than that of pediatric ACC worldwide. Because childhood ACC is associated with Li-Fraumeni syndrome, we examined the cancer history and p53 status of 36 Brazilian patients and their families. Remarkably, 35 of 36 patients had an identical germ-line point mutation of p53 encoding an R337H amino acid substitution. Differences within intragenic polymorphic markers demonstrated that at least some mutant alleles arose independently, thus eliminating a founder effect. In tumor cells, the wild-type allele was deleted, and mutant p53 protein accumulated within the nuclei. Although these features are consistent with Li-Fraumeni syndrome-associated adrenal tumors, there was no history of increased cancer incidence among family members. Therefore, this inherited R337H p53 mutation represents a low-penetrance p53 allele that contributes in a tissue-specific manner to the development of pediatric ACC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genes p53
/
Mutação Puntual
/
Neoplasias do Córtex Suprarrenal
/
Mutação em Linhagem Germinativa
Limite:
Child
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article