Intra- And intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing

Tumor heterogeneity is a major obstacle to the success of cancer treatment. An accurate understanding and recognition of tumor heterogeneity is critical in the clinica management of cancer patients. Here, we utilized single-cell RNA sequencing (scRNA seq) to uncover the intra- and intertumoral heterogeneity of liver metastases from a patien with metastatic uveal melanoma. The two metastases analyzed were largely infiltrated by noncancerous cells with significant variability in the proportion of different cell types Analysis of copy-number variations (CNVs) showed gain of 8q and loss of 6q in both tumors but loss of Chromosome 3 was only detected in one of the tumors. Single-nucleotide poly morphism (SNP) array revealed a uniparental isodisomy 3 in the tumor with two copies o Chromosome 3, indicating a regain of Chromosome 3 during the development of the met astatic disease. In addition, both tumors harbored subclones with additional CNVs. Pathway enrichment analysis of differentially expressed genes revealed that cancer cells in the me tastasis with isodisomy 3 showed up-regulation in epithelial–mesenchymal transition and myogenesis related genes. In contrast, up-regulation in interferon signaling was observed in the metastasis with monosomy 3 and increased T-cell infiltrate. This study highlights the complexity and heterogeneity of different metastases within an individual case of uvea melanoma. © 2021 Lin et al.