An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma

Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9330-5. doi: 10.1073/pnas.161479898.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex Neoplasms / genetics*
  • Base Sequence
  • Cell Nucleus / metabolism
  • Child
  • DNA Primers
  • Female
  • Genes, p53*
  • Germ-Line Mutation*
  • Humans
  • Loss of Heterozygosity
  • Male
  • Pedigree
  • Point Mutation*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • DNA Primers
  • Tumor Suppressor Protein p53