Germline TP53 mutations are observed in ∼80% of patients with Li-Fraumeni syndrome (LFS) and a lesser frequency of patients meeting the revised Chompret criteria. A variety of studies are being conducted exploring the role of genetic modifiers on p53 function and their impact in refining the genotype:phenotype correlation of the TP53:LFS relationship. In this presentation, four classical pediatric-onset LFS tumors (choroid plexus carcinoma, medulloblastoma, adrenocortical carcinoma and rhabdomyosarcoma) will be used as examples to demonstrate the molecular nuances of this complex relationship. A spectrum of findings will be outlined that support the notion that presence of a germline TP53 mutation in the context of different modifying effects of intragenic TP53 polymorphism as well as variants in genes and proteins that play important roles in the p53 network confers certain biological features to the presentation of these tumors. Biological mechanisms will be discussed and strategies for early cancer detection will be presented.

Citation Format: Jonathan Wasserman, Anita Villani, Nardin Samuel, Diana Merino, Ana Novokmet, Margaret Pienkowska, Badr IdSaid, David Malkin. Li-Fraumeni syndrome: p53 and beyond. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr IA10. doi:10.1158/1538-7445.CANSUSC14-IA10

©2014 American Association for Cancer Research.
2014