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Single-cell sequencing of genomic DNA resolves sub-clonal heterogeneity in a melanoma cell line.

Published version
Peer-reviewed

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Type

Article

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Authors

Velazquez-Villarreal, Enrique I 
Maheshwari, Shamoni 
Sorenson, Jon 
Fiddes, Ian T 
Kumar, Vijay 

Abstract

We performed shallow single-cell sequencing of genomic DNA across 1475 cells from a cell-line, COLO829, to resolve overall complexity and clonality. This melanoma tumor-line has been previously characterized by multiple technologies and is a benchmark for evaluating somatic alterations. In some of these studies, COLO829 has shown conflicting and/or indeterminate copy number and, thus, single-cell sequencing provides a tool for gaining insight. Following shallow single-cell sequencing, we first identified at least four major sub-clones by discriminant analysis of principal components of single-cell copy number data. Based on clustering, break-point and loss of heterozygosity analysis of aggregated data from sub-clones, we identified distinct hallmark events that were validated within bulk sequencing and spectral karyotyping. In summary, COLO829 exhibits a classical Dutrillaux's monosomic/trisomic pattern of karyotype evolution with endoreduplication, where consistent sub-clones emerge from the loss/gain of abnormal chromosomes. Overall, our results demonstrate how shallow copy number profiling can uncover hidden biological insights.

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Keywords

Cell Line, Tumor, DNA Copy Number Variations, Humans, Karyotyping, Loss of Heterozygosity, Melanoma, Sequence Analysis, DNA, Single-Cell Analysis

Journal Title

Commun Biol

Conference Name

Journal ISSN

2399-3642
2399-3642

Volume Title

3

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research Uk (None)