title: Towards an understanding of the role of p53 in adrenocortical carcinogenesis.
abstract: Adrenocortical carcinoma (ACC) is recognized to be a component tumor of the Li Fraumeni Syndrome (LFS), a familial cancer predisposition resulting from germline mutations in the p53 tumor-suppressor. p53 activity is tightly regulated by multiple post-translational mechanisms, disruption of which may lead to tumorigenesis. ACC is present in disproportionately high rates among p53-mutation carriers, suggesting tissue-specific manifestations of p53 deficiency. Additionally, p53-associated ACC demonstrates a strong predominance in infants and children. Several of the p53 alleles associated with pediatric ACC, however, retain significant wild-type activity and demonstrate incomplete penetrance, a finding distinct from other LFS-component tumors. In this review, we discuss the relationship between p53 and adrenocortical carcinogenesis, with specific focus on disease-specific alleles, tumorigenesis in the context of adrenal development and potential therapeutic approaches to p53-associated ACC.
authors.affiliation: Division of Endocrinology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8. Jonathan.Wasserman@sickkids.ca
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wasserman
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Zambetti
authors.forename: David
authors.initials: D
authors.lastname: Malkin
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000483:Alleles; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D016864:Li-Fraumeni Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009928:Organ Specificity; D019683:Penetrance; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53