Single-cell sequencing of genomic DNA resolves sub-clonal heterogeneity in a melanoma cell line
| Autor: | Jon Sorenson, Vijay Kumar, Yifeng Yin, John D. Carpten, Shamoni Maheshwari, Enrique I. Velazquez-Villarreal, Mira Grigorova, Ian T. Fiddes, Claudia Catalanotti, Michelle Webb, David Craig, Paul A.W. Edwards |
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| Přispěvatelé: | Edwards, Paul A. [0000-0002-4789-3374], Carpten, John D. [0000-0002-6862-2821], Apollo - University of Cambridge Repository, Edwards, Paul A [0000-0002-4789-3374], Carpten, John D [0000-0002-6862-2821] |
| Rok vydání: | 2020 |
| Předmět: |
DNA Copy Number Variations
Somatic cell Tumour heterogeneity Medicine (miscellaneous) Loss of Heterozygosity 45/23 Computational biology 631/67/69 Biology 631/67/2329 General Biochemistry Genetics and Molecular Biology Loss of heterozygosity 03 medical and health sciences 0302 clinical medicine Cell Line Tumor 631/67/68 Cancer genomics Endoreduplication Humans 631/208/68 631/208/69 Cluster analysis lcsh:QH301-705.5 Cancer genetics Melanoma 030304 developmental biology 0303 health sciences 45 article Karyotype Sequence Analysis DNA genomic DNA lcsh:Biology (General) Single cell sequencing Karyotyping Principal component analysis Single-Cell Analysis General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Communications Biology Communications Biology, Vol 3, Iss 1, Pp 1-8 (2020) |
| Popis: | 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. Through shallow single-cell sequencing of genomic DNA followed by clustering analysis, Velazquez-Villarreal et al. reveal sub-clones of the melanoma cell line COLO829 and further identify and validate chromosome translocations and copy number changes. This study illustrates how copy number variation analysis can provide insights into cancer cell heterogeneity. |
| Databáze: | OpenAIRE |
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