Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing.
Cold Spring Harb Mol Case Stud
; 7(5)2021 10.
Article
en En
| MEDLINE
| ID: mdl-34470851
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Úvea
/
Neoplasias Hepáticas
/
Melanoma
Límite:
Humans
Idioma:
En
Revista:
Cold Spring Harb Mol Case Stud
Año:
2021
Tipo del documento:
Article
País de afiliación:
Australia