P53-dependent Metabolic and Epigenetic Reprogramming in Carcinogenesis

Informations projet

MetEpiC

N° de convention de subvention: 846806

DOI

10.3030/846806

Projet clôturé

Date de signature de la CE 10 Avril 2019

Date de début 1 Avril 2020

Date de fin 31 Mai 2022

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 196 707,84

Contribution de l’UE

€ 196 707,84

Coordonné par

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

Periodic Reporting for period 1 - MetEpiC (P53-dependent Metabolic and Epigenetic Reprogramming in Carcinogenesis)

Période du rapport: 2020-04-01 au 2022-03-31

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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.

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