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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 clinical management of cancer patients. Here, we utilized single-cell RNA sequencing (scRNA-seq) to uncover the intra- and intertumoral hete...

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Autores principales: Lin, Weitao, Beasley, Aaron B., Ardakani, Nima Mesbah, Denisenko, Elena, Calapre, Leslie, Jones, Matthew, Wood, Benjamin A., Warburton, Lydia, Forrest, Alistair R. R., Gray, Elin S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559622/
https://www.ncbi.nlm.nih.gov/pubmed/34470851
http://dx.doi.org/10.1101/mcs.a006111
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author Lin, Weitao
Beasley, Aaron B.
Ardakani, Nima Mesbah
Denisenko, Elena
Calapre, Leslie
Jones, Matthew
Wood, Benjamin A.
Warburton, Lydia
Forrest, Alistair R. R.
Gray, Elin S.
author_facet Lin, Weitao
Beasley, Aaron B.
Ardakani, Nima Mesbah
Denisenko, Elena
Calapre, Leslie
Jones, Matthew
Wood, Benjamin A.
Warburton, Lydia
Forrest, Alistair R. R.
Gray, Elin S.
author_sort Lin, Weitao
collection PubMed
description Tumor heterogeneity is a major obstacle to the success of cancer treatment. An accurate understanding and recognition of tumor heterogeneity is critical in the clinical 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 patient 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 polymorphism (SNP) array revealed a uniparental isodisomy 3 in the tumor with two copies of Chromosome 3, indicating a regain of Chromosome 3 during the development of the metastatic disease. In addition, both tumors harbored 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, 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 uveal melanoma.
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spelling pubmed-85596222021-11-10 Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing Lin, Weitao Beasley, Aaron B. Ardakani, Nima Mesbah Denisenko, Elena Calapre, Leslie Jones, Matthew Wood, Benjamin A. Warburton, Lydia Forrest, Alistair R. R. Gray, Elin S. Cold Spring Harb Mol Case Stud Research Report Tumor heterogeneity is a major obstacle to the success of cancer treatment. An accurate understanding and recognition of tumor heterogeneity is critical in the clinical 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 patient 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 polymorphism (SNP) array revealed a uniparental isodisomy 3 in the tumor with two copies of Chromosome 3, indicating a regain of Chromosome 3 during the development of the metastatic disease. In addition, both tumors harbored 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, 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 uveal melanoma. Cold Spring Harbor Laboratory Press 2021-10 /pmc/articles/PMC8559622/ /pubmed/34470851 http://dx.doi.org/10.1101/mcs.a006111 Text en © 2021 Lin et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
spellingShingle Research Report
Lin, Weitao
Beasley, Aaron B.
Ardakani, Nima Mesbah
Denisenko, Elena
Calapre, Leslie
Jones, Matthew
Wood, Benjamin A.
Warburton, Lydia
Forrest, Alistair R. R.
Gray, Elin S.
Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing
title Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing
title_full Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing
title_fullStr Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing
title_full_unstemmed Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing
title_short Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing
title_sort intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell rna sequencing
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559622/
https://www.ncbi.nlm.nih.gov/pubmed/34470851
http://dx.doi.org/10.1101/mcs.a006111
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