A 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 Bra zil is 10-15 times higher than that of pediatric ACC worldwide. Because chi ldhood ACC is associated with Li-Fraumeni syndrome, we examined the cancer history and p53 status of 36 Brazilian patients and their families. Remarka bly, 35 of 36 patients had an identical germ-line point mutation of p53 enc oding an R337H amino acid substitution. Differences within intragenic polym orphic markers demonstrated that at least some mutant alleles arose indepen dently, thus eliminating a founder effect. In tumor cells, the wild-type al lele was deleted, and mutant p53 protein accumulated within the nuclei. Alt hough these features are consistent with Li-Fraumeni syndrome-associated ad renal tumors, there was no history of increased cancer incidence among fami ly members. Therefore, this inherited R337H p53 mutation represents a low-p enetrance p53 allele that contributes in a tissue-specific manner to the de velopment of pediatric ACC.