Integrated Genomics of Pediatric Cancers

Our emerging team, supported by the ATIP-Avenir program of Inserm and the CNRS, is launching studies aimed at understanding the biological mechanisms that enable certain tumor cells to survive treatment and lead to treatment relapse in pediatric cancers, particularly in acute childhood leukemias.

A central challenge for us is to answer a fundamental question in pediatric oncology: how does the cellular state of tumor cells—including aspects related to development—create an environment that allows genetic alterations to take hold and spread, ultimately leading to cancer?

Pediatric cancers, particularly leukemias, generally exhibit low genetic complexity, suggesting that the mechanisms that increase the risk of—or cause—progression and relapse do not rely solely on the accumulation of mutations. As such, we propose to study the clonal dynamics of the disease in light of the specific cellular states that enable a cell to become functionally cancerous.

Our objectives are twofold: (1) fundamental, to understand the clonal evolution of the disease through the lens of cellular states interacting with the disease’s genetics, and (2) clinical, by identifying cell populations that may be responsible for resistance and relapse.

This new, emerging team proposes a vision of tumor evolution driven by cellular identity. Ultimately, our work could help identify cells at risk of relapse at the time of diagnosis, improve risk stratification for patients, guide the development of therapeutic strategies targeting specific cellular states, and contribute to improving the prognosis for children with cancer.