scDNA-seq for 'Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma'
Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.
- 1416 samples
- DAC: EGAC00001000534
- Technology: Illumina NovaSeq 6000
Data Access Policy for data generated by the Gisselsson Group at the Department of Clinical Genetics, Lund University.
The data access agreement provided by the data access committee stipulates that in order to get access to the deposited genetic data, the user will need to agree to: • use the data only for academic research purposes; • cite the original article in any resulting publication; • protect the confidentiality of the data; • provide appropriate data security; • not attempt to identify individual participants from whom data were obtained; • not redistribute the data, or any subset or derivative, that could be used to identify the research participant
Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
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| Other |