Endocrine Abstracts

Li Fraumeni syndrome (LFS) is a prototypic cancer predisposition syndrome, characterized by multiple, early-onset malignant tumours including breast cancer, bone and soft tissue sarcomas, brain tumors and adrenocortical carcinoma (ACC). LFS is most commonly attributed to germline mutations in the TP53 tumor-suppressor gene. p53 activity is tightly regulated by multiple post-translational mechanisms, disruption of which may lead to tumorigenesis. ACC occurs at 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 retain significant wild-type activity and demonstrate incomplete penetrance, a finding distinct from other LFS-component tumors. This presentation will evaluate current knowledge of 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. In addition, evaluation of the implementation of a clinical surveillance protocol for early tumor detection will be discussed. The example of LFS as a paradigm of translation from molecular testing to clinical intervention will be highlighted in this session.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.