Division of Endocrinology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada M5G 1X8; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
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.
Written by:
Wasserman JD, Zambetti GP, Malkin D. Are you the author?
Reference: Mol Cell Endocrinol. 2011 Sep 10. Epub ahead of print.
doi: 10.1016/j.mce.2011.09.010
PubMed Abstract
PMID: 21930187
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