ATRT
Conditions
Keywords
ATRT, SMARCB1, single-cell RNAseq
Brief summary
The aim is to describe at the cellular level the heterogeneity of rhabdoid tumors, and identify how this diversity influences resistance to treatment.
Detailed description
Rhabdoid tumors are aggressive cancers of infancy. Although frequently chemosensitive at the very beginning, they very often show resistance, suggesting some intra-tumor diversity or plasticity. Moreover, morphological analysis of rhadoid tumors often reveal some variety in tumor cell shapes and immunohistochemical profiling. Altogether, this suggests some intra-tumor heterogeneity, that has been scarcely studied so far. This project aims to describe the intra-tumor heterogeneity by single-cell sequencing approaches. After surgical resection, fresh tumor samples will be dissected and analysed using the 10X Chromium technology. Briefly, cells will be grouped in clusters according to their gene expression signalling, and each cluster will be defined in comparison with all other ones. Differential analyses will allow identifying the main characteristic of each cell sub-population. Potential filiations between clusters will be analysed using classical algorithms. The study will be performed on 10 to 15 tumor samples.
Interventions
BIOLOGICALanalyzes in singles cells
genome expression analyzes in single cells
Sponsors
Institut Curie
URC-CIC Paris Descartes Necker Cochin
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* Aged 0-17 years old * having a rhabdoid tumor according to clinical and radiological features Or likely having a rhabdoid tumor according to clinical and radiological features * surgical resection in standard care * sufficient material for both diagnosis and experimental procedures * parents' agreement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intra-tumor heterogeneity | Inclusion | Identification of cell clusters - mean expression (RPKM unit) of gene set signtaures in each bioinformatically defined cluster |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cell clusters recurrent from one sample to the other | Inclusion | Fraction/percentage of cell clusters defined by primary outcome that are specific to each tumor and those that are shared by several or all samples |
| Naming of potential targetable gene | Inclusion | Mean expression (RPKM unit) of targetable genes (defined by the existence of adequate pharmacological inhibitor) in each tumor sample and clusters |
| Identification of cytotoxic cells | Inclusion | Conducting therapeutic biological functional tests |
Countries
France
Outcome results
None listed