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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\u00a0insight. 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\u2019s 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.<\/jats:p>","DOI":"10.1038\/s42003-020-1044-8","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T10:03:15Z","timestamp":1593079395000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Single-cell sequencing of genomic DNA resolves sub-clonal heterogeneity in a melanoma cell line"],"prefix":"10.1038","volume":"3","author":[{"given":"Enrique I.","family":"Velazquez-Villarreal","sequence":"first","affiliation":[]},{"given":"Shamoni","family":"Maheshwari","sequence":"additional","affiliation":[]},{"given":"Jon","family":"Sorenson","sequence":"additional","affiliation":[]},{"given":"Ian T.","family":"Fiddes","sequence":"additional","affiliation":[]},{"given":"Vijay","family":"Kumar","sequence":"additional","affiliation":[]},{"given":"Yifeng","family":"Yin","sequence":"additional","affiliation":[]},{"given":"Michelle G.","family":"Webb","sequence":"additional","affiliation":[]},{"given":"Claudia","family":"Catalanotti","sequence":"additional","affiliation":[]},{"given":"Mira","family":"Grigorova","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4789-3374","authenticated-orcid":false,"given":"Paul A.","family":"Edwards","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-2821","authenticated-orcid":false,"given":"John D.","family":"Carpten","sequence":"additional","affiliation":[]},{"given":"David W.","family":"Craig","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"1044_CR1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/nature08658","volume":"463","author":"ED Pleasance","year":"2010","unstructured":"Pleasance, E. 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