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

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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.



Article, /631/67/2329, /631/208/68, /631/208/69, /631/67/68, /631/67/69, /45, /45/23, article

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Communications Biology

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Nature Publishing Group UK