Document Type

Journal Article

Publication Title

Cold Spring Harbor Molecular Case Studies


Cold Spring Harbor Laboratory Press


School of Medical and Health Sciences / Centre for Precision Health




National Health and Medical Research Council

Grant Number

NHMRC Number : APP1154524, APP1190643


Lin, W., Beasley, A. B., Ardakani, N. M., Denisenko, E., Calapre, L., Jones, M., ... & Gray, E. S. (2021). Intra-and inter-tumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing. Molecular Case Studies, mcs-a006111.


Tumour heterogeneity is a major obstacle to the success of cancer treatment. An accurate understanding and recognition of tumour heterogeneity is critical in the clinical management of cancer patients. Here, we utilised single-cell RNA sequencing (scRNA-seq) to uncover the intra- and inter-tumoural heterogeneity of liver metastases from a patient with metastatic uveal melanoma. The two metastases analysed were largely infiltrated by non-cancerous 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 tumours, but loss of chromosome 3 was only detected in one of the tumours. SNP array revealed a uniparental isodisomy 3 in the tumour with two copies of chromosome 3, indicating a re-gain of chromosome 3 during the development of the metastatic disease. In addition, both tumours harboured subclones with additional CNVs. Pathway enrichment analysis of differentially expressed genes revealed that cancer cells in the metastasis with isodisomy 3 showed up-regulation in epithelial-mesenchymal transition and myogenesis related genes. In contrast, upregulation in interferon signalling 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 uveal melanoma.



Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License