Deciphering intra-tumoral and temporal heterogeneity in IDH mutant gliomas brain tumors

This project aims to identify and study the cancer master regulators in two major, understudied contexts: temporal heterogeneity, specifically in the setting of recurrent disease, and intra-tumoral heterogeneity (ITH) in high-grade gliomas. These types of heterogeneity are of critical clinical importance since they represent two major causes of treatment failure.

In this project, we are generating and analysing single-nucleus RNA-seq data (snRNA-seq) of primary-recurrent pairs of IDH mutant glioma tumors which are understudied but common high-grade gliomas in younger adults. Analyzing tumors at the single-cell resolution, we will reveal the master regulators’ tumor cell populations and evaluate the ITH. In addition, we will identify the cell of origin of the recurrent tumor, then propose drug targets for the initiating recurrent cells and the recurrent tumor. Overall, this project will provide novel biological insights into cancer heterogeneity at the level of master transcriptional regulators that will lead to further development of preclinical models and novel rationales for therapeutic targeting.

Collaboration: Pr. F. Ducray (The Cancer Research Center of Lyon (CRCL) & University Hospital of Lyon (HCL))