The aim is to describe at the cellular level the heterogeneity of rhabdoid tumors, and identify how this diversity influences resistance to treatment.
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.
Study Type
OBSERVATIONAL
Enrollment
15
genome expression analyzes in single cells
Institut Curie
Paris, France
Intra-tumor heterogeneity
Identification of cell clusters - mean expression (RPKM unit) of gene set signtaures in each bioinformatically defined cluster
Time frame: Inclusion
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
Time frame: 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
Time frame: Inclusion
Identification of cytotoxic cells
Conducting therapeutic biological functional tests
Time frame: Inclusion
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