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Tuesday, May 14th, 2019
From 14h To 15h
Centre de Recherche - Paris - Amphith√©√Ętre Marie Curie

Li-Fraumeni Syndrome: What are the challenges and opportunities 50 years after the first report?

More than 85% of patients with Li-Fraumeni syndrome harbour germline TP53 mutations. The spectrum of mutations and the heterogeneity of tumor presentation (age of onset and type) within and between families is remarkable, and indicates that modifiers must play an important role in defining the phenotype of each patient and each family. We recently reported the feasibility and utility of a clinical surveillance protocol for early detection of tumours in TP53 mutation carriers (Villani et al Lancet Oncol 2016). Results from deep sequencing of both the genome and epigenome of mutation carriers provide exciting insight into the role of modifiers on both the functional activity of p53 in the germline as well as their influence on tumor onset, tumor spectrum and clinical outcome/response to therapy. Data will be presented to support the creation of molecular algorithms that may be used in a precise manner that reflects the unique genetic and epigenetic signature of LFS patients. It is anticipated that these algorithms can then be used to more effectively refine and guide the creation of personalized and precise surveillance strategies for these patients. Furthermore, application of these unique signatures to in vitro and in vivo models of p53 dysfunction offer insight into novel chempreventive strategies to defer or prevent tumor onset in patients.


Dr. David Malkin

Invited by

Dr. Olivier Delattre