Description

Liposarcomas (LPS) are soft tissue tumours of mesenchymal origin. The most common histological subtypes, represented by well differenciated Lipsarcomas (WD-LPS) and dedifferenciated (DD-LPS), are characterized by the quasi-systematic amplification of the q13-15 of chromosome 12 containing the Mdm2 gene.

The systematic amplification of the Mdm2 gene is such that it is used clinically to distinguish WD/DD-LPS from other types of sarcomas. These observations raise key questions about the high selection pressure that leads to the almost systematic amplification of Mdm2 during the development of these LPS.

Mdm2 is an oncoprotein whose roles in p53 tumour suppressor degradation are broadly described. However, the different inhibitors targeting this interaction were disappointing in clinical trials.

Recently a team from the U1194 INSERM unit of the IRCM which collaborates in this project showed by a pan-genomics analysis, that Mdm2 is recruited to chromatin within a multiproteic complex having as target a transcriptional program involved in the metabolism and in particular in the biosynthesis of the serin.

This clinical-biological basis will allow the continuation of this research project on liposarcomas and the development of new research projects on other histological types of sarcomas.