Single-cell sequencing of genomic DNA resolves sub-clonal heterogeneity in a melanoma cell line
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Velazquez-Villarreal, Enrique I.
Fiddes, Ian T.
Webb, Michelle G.
Craig, David W.
Nature Publishing Group UK
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Velazquez-Villarreal, E. I., Maheshwari, S., Sorenson, J., Fiddes, I. T., Kumar, V., Yin, Y., Webb, M. G., et al. (2020). Single-cell sequencing of genomic DNA resolves sub-clonal heterogeneity in a melanoma cell line. Communications Biology, 3 (1) https://doi.org/10.1038/s42003-020-1044-8
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.
Article, /631/67/2329, /631/208/68, /631/208/69, /631/67/68, /631/67/69, /45, /45/23, article
External DOI: https://doi.org/10.1038/s42003-020-1044-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317793
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/