Société Française de Bioinformatique

Mots-Clés

RNA-seq spatial transcriptomics bladder cancer

Description

Sarcomatoid urothelial carcinoma is a rare and aggressive morphological subtype of bladder cancer. Through the analysis of a mouse model and public transcriptomic datasets of human tumors, we have previously shown that this subtype shows FGFR1 pathway activation and features of epithelial-to-mesenchymal transition (Fontugne et al. J Pathol 2023 PMID: 36695554). Bladder cancer is characterized by morphological heterogeneity. It has been suggested that sarcomatoid tumors arise from the progression and dedifferentiation of previous or adjacent non-sarcomatoid component.
The goal of this project is to characterize the mechanisms of sarcomatoid urothelial carcinoma dedifferentiation through a multisampling and comparative multi-omics approach and further in situ and functional validations.
We have constituted a cohort of 45 patients with sarcomatoid urothelial carcinoma for which transcriptomic profiling (bulk 3’ RNA-seq) from paired sarcomatoid and non-sarcomatoid component samples is now available. Spatial transcriptomics of a mouse model and human tumors with both sarcomatoid and non-sarcomatoid areas will also be available. Whole exome sequencing and methylation profiles of both sarcomatoid and non-sarcomatoid components may be obtained.
The comparative analyses between sarcomatoid and matched non-sarcomatoid samples will further our understanding of sarcomatoid tumor carcinogenesis and identify potential new therapeutic targets for this aggressive disease.
The Master 2 student will analyze this multi-omics data using existing bioinformatic tools (R, Python) and contribute to the validation of the new potential therapeutic targets. The project will be carried out within the Molecular Oncology team at Institut Curie in Paris, surrounded by bioinformaticians, experimental biologists and medical doctors.