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To this regard, mesenchymal neoplasms are particularly challenging due to the combination of their rarity and the large number of subtypes, and many entities still lack robust diagnostic hallmarks. RNA transcriptomic profiles have proven to be a reliable basis for the classification of previously unclassified tumors and notably for mesenchymal neoplasms. Using exome\u2010based RNA capture sequencing on more than 5000 samples of archival material (formalin\u2010fixed, paraffin\u2010embedded), the combination of expression profiles analyzes (including several clustering methods), fusion genes, and small nucleotide variations has been developed at the Centre L\u00e9on B\u00e9rard (CLB) in Lyon for the molecular diagnosis of challenging neoplasms and the discovery of new entities. 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