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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-06-25

AUTHORS

Enrique I. Velazquez-Villarreal, Shamoni Maheshwari, Jon Sorenson, Ian T. Fiddes, Vijay Kumar, Yifeng Yin, Michelle G. Webb, Claudia Catalanotti, Mira Grigorova, Paul A. Edwards, John D. Carpten, David W. Craig

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. More... »

PAGES

318

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s42003-020-1044-8

DOI

http://dx.doi.org/10.1038/s42003-020-1044-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1128745772

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32587328


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