An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma.
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.
Ribeiro
R C
RC
Department of Hematology-Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA. raul.ribeiro@stjude.org
Sandrini
F
F
Figueiredo
B
B
Zambetti
G P
GP
Michalkiewicz
E
E
Lafferty
A R
AR
DeLacerda
L
L
Rabin
M
M
Cadwell
C
C
Sampaio
G
G
Cat
I
I
Stratakis
C A
CA
Sandrini
R
R
D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D017931:DNA Primers; D005260:Female; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D017931:DNA Primers; D016159:Tumor Suppressor Protein p53