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Velazquez-Villarreal, Enrique I; Maheshwari, Shamoni; Sorenson, Jon; Fiddes, Ian T; Kumar, Vijay; Yin, Yifeng; Webb, Michelle G; Catalanotti, Claudia; Grigorova, Mira; Edwards, Paul A; Carpten, John D; Craig, David W
Communications biology, 06/2020, Volume: 3, Issue: 1Journal Article
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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