Periodic Reporting for period 1 - MetEpiC (P53-dependent Metabolic and Epigenetic Reprogramming in Carcinogenesis)
Reporting period: 2020-04-01 to 2022-03-31
Cancer is a multifactorial and complex disease, but some alterations are frequently observed in tumors. Mutations of the tumor suppressor gene TP53, a guardian of our cells, are the most frequent alterations in cancers cells, with about half of tumors harboring this mutational event. Moreover, heritable TP53 mutations leads to predisposition to early, rare and multiple cancers in patients, a condition referred as the Li-Fraumeni Syndrome. The project aimed at characterizing downstream events associated with TP53 mutations, using state-of-the-art omics technologies, in order to find molecular signatures that could participate to cancer development and to seek for cancer biomarkers and drug targets. Cancer represent a major cause of death in our society, thus it is crucial to better understand the causes of cancer development and to find therapeutic options that will improve cancer care management in the future.
My first activity was to use online available omic data of 33 different types of cancers, to find signatures associated with TP53 mutations. Interestingly, common patterns of signatures were found across cancer types. Then, I was able to determine that signatures were conserved in cells of patients with Li-Fraumeni Syndrome carrying germinal mutations of TP53. Finally, I conducted a study to propose a new classification of the TP53 mutations, aiming at better predict cancer susceptibility in Li-Fraumeni patients, and effects of TP53 mutations in cancers in general. These findings are currently under preparation for dissemination to the scientific community and the general public.
Thanks to this project, I have better characterized the molecular misregulations associated with TP53 mutations in cancers and in Li-Fraumeni Syndrome population. This will serve as a base to propose biomarkers and therapeutic strategies for patients with cancers. Moreover, the newly proposed classification of TP53 mutations will help to stratify patients suffering from Li-Fraumeni Syndrome, and will better predict cancer risks in this population.