Methods and compositions for predicting and treating uveal melanoma

Here, in multi-scale analyses using single-cell RNA sequencing of six different primary uveal melanomas, inventors uncover a previously unrecognized intratumor heterogeneity at the genetic and transcriptomic level. They identify distinct transcriptional cell states and diverse tumor-associated populations in a subset of primary uveal melanomas. They also decipher a gene regulatory network underlying an invasive and poor prognosis state driven in part by the transcription factor HES6, a member of the NOTCH signaling pathway. HES6 heterogenous expression has been validated by RNAscope assays within primary uveal melanomas, which unveils the existence of these cells conveying a dismal prognosis in tumors diagnosed with a favorable outcome using bulk analyses. Depletion of HES6 impairs growth, migration and metastatic dissemination, demonstrating essential roles of HES6 in uveal melanoma progression.

Keywords: Uveal Melanoma, RNA Signatures, Prognosis, Intratumoral heterogeneity
Patent Application number: EP20 306 385.4 on 16/11/2020
Publications:
Cell Death Differ. 2021 Jun 28 Pandiani et al Single-cell RNA sequencing reveals intratumoral heterogeneity in primary uveal melanomas and identifies HES6 as a driver of the metastatic disease. DOI: 10.1038/s41418-020-00730-7 Prog Retin Eye Res 2021 Apr 13 Strub et al Translation of single-cell transcriptomic analysis of uveal melanomas to clinical oncology DOI: 10.1016/j.preteyeres.2021.100968

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