Rhabdoid Tumors Cellular Architecture by Single-cell Analyses (InnovRT-2)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Hétérogénéité Des Tumeurs Rhabdoides : Approches en  Cellules Uniques  Pour Identifier Des Cibles thérapeutiques

Conditions
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ATRT

Intervention / Treatment
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* Biological: analyzes in singles cells


Participation Criteria
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Eligibility Criteria
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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 health insurance

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ATRT<br>Children affected by an ATRT at time of surgical resection | Biological: analyzes in singles cells<br>* genome expression analyzes in single cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-tumor heterogeneity | Identification of cell clusters - mean expression (RPKM unit) of gene set signtaures in each bioinformatically defined cluster | Inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cell clusters recurrent from one sample to the other | 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 | Inclusion | 
| Naming of potential targetable gene | Mean expression (RPKM unit) of targetable genes (defined by the existence of adequate pharmacological inhibitor) in each tumor sample and clusters | Inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ATRT, SMARCB1, single-cell RNAseq