An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma
Authors:
- Raul C. RibeiroRRRaul C. Ribeiro
- Fabiano SandriniFSFabiano Sandrini
- Bonald FigueiredoBFBonald Figueiredo
- Gerard P. ZambettiGZGerard P. Zambetti
- Edson MichalkiewiczEMEdson Michalkiewicz
- Antony R. LaffertyALAntony R. Lafferty
- Luiz DeLacerdaLDLuiz DeLacerda
- Mark RabinMRMark Rabin
- Craig CadwellCCCraig Cadwell
- Gilberto SampaioGSGilberto Sampaio
- Israil CatICIsrail Cat
- Constantine A. StratakisCSConstantine A. Stratakis
Top Cited Papers
- 31 July 2001
- journal article
- Published by National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 98 (16) , 9330-9335
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.Keywords
This publication has 37 references indexed in Scilit:
- Are There Low-Penetrance TP53 Alleles? Evidence from Childhood Adrenocortical TumorsThe American Journal of Human Genetics, 1999
- Cancer phenotype correlates with constitutional TP53 genotype in families with the Li–Fraumeni syndromeOncogene, 1998
- Characterization of the oligomerization defects of two p53 mutants found in families with Li–Fraumeni and Li–Fraumeni-like syndromeOncogene, 1998
- Genetic and functional studies of a germline TP53 splicing mutation in a Li–Fraumeni-like familyOncogene, 1998
- DNA analysis at p53 locus in carcinomas arising from pleomorphic adenomas of salivary glands: Comparison of molecular study and p53 immunostainingPathology International, 1998
- Developmental and Functional Biology of the Primate Fetal Adrenal CortexEndocrine Reviews, 1997
- Two functional assays employed to detect an unusual mutation in the oligomerisation domain of p53 in a Li-Fraumeni like familyOncogene, 1997
- In vitro synthesis of novel genes: mutagenesis and recombination by PCR.Genome Research, 1994
- Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element.Genes & Development, 1992
- Detection of Novel Germ-line p53 Mutations in Diverse-Cancer-Prone Families Identifiled by Selecting Patients With Childhood Adrencortical CarcinomaJNCI: Journal of the National Cancer Institute, 1992