Tumor cell identity and plasticity

Neuroblastoma
I Janoueix-Lerosey, G Schleiermacher and O Delattre
Background: A study of tumor heterogeneity revealed that most neuroblastomas are made up of cells with a noradrenergic precursor phenotype. However, a minority of cells present a completely different epigenetic profile associated with a neural crest type identity. These two cell types co-exist within tumors in variable proportions. Preliminary data from the team suggest that tumor cells have the capacity to shift from one identity to the other.
Hypothesis: Target only one of these two cell types could be insufficient to treat the disease.
Objective: Study cell plasticity in neuroblastoma:
- Modulate the expression of key cell actors in the regulatory circuits of genes involved in these identity changes and observe the impact of these modulations on the cell phenotype.
- Study cell heterogeneity in tumors with identity-specific biomarkers.
- Evaluate the impact of treatment of each individual cell type
Find out more about cell plasticity in neuroblastoma (in French)
Ewing sarcoma
D Surdez and O Delattre
Background: Ewing sarcoma is generally characterized by a fusion between the EWS1 and FLI1 genes. This gene fusion leads to the formation of a chimeric protein EWS1-FLI. This chimeric protein acts on the genome in different places. The team has recently demonstrated that the variation of the EWS-FLI1 protein expression level had a considerable impact on the features of Ewing cells. EWS-FLI1low: the cells have a mesenchymal stem cell phenotype and can migrate while the EWS-FLI1high proliferate. The shift between these two states is completely reversible.
Hypothesis: A better understanding of the transition mechanism between these two states could have repercussions on therapeutic management.
Objective: Study cell mechanisms responsible for the variations in the EWS-FLI1 level from one cell to another. We will focus on the impact of treatments on the level of EWS-FLI1 and on the impact of STAG2 mutations on cell plasticity.
Retinoblastoma
F Radvanyi
Background: Retinoblastoma is a disease made up of two sub-types: the first tumor sub-type expresses cone cell markers, the second sub-type presents an intra-tumor heterogeneity expressing, often exclusively, markers of different cell types in the retina suggesting a multi-cell origin for these tumors.
Hypothesis: tumor heterogeneity and plasticity could be responsible for treatment resistance
Objective: Obtain a better characterization of inter and intra-tumor heterogeneity and better understand plasticity