Methods and compositions for predicting and treating uveal melanoma

Abstract

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 diversetumor-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.

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