Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-24870-7
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Funding
- Swedish Research Council [2016-07213, 2018-05973]
- Swedish Research Council
- Swedish Childhood Cancer Fund
- Swedish Cancer Society
- Knut and Alice Wallenberg Foundation
- ParaDiff Foundation
- ERC Synergy grant (KILL-OR-DIFFERENTIAT)
- Swedish Foundation for Strategic Research
- ERC Consolidator grant (STEMMING-FROM-NERVE)
- Paradifference Foundation
- Bertil Hallsten Research Foundation
- Cancer Foundation in Sweden
- [NSF-14-532]
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The study shows that childhood neuroblastoma can be separated into high and low risk groups with different cell identities and malignancy potential, indicating two distinct disease entities. Low-risk neuroblastoma resembles sympatho- and chromaffin cells in terms of transcriptome, while the malignant cells in high-risk neuroblastoma resemble a subtype of cholinergic progenitor population in human post-natal gland. The findings reveal different gene expression programs for worst and better survival in correlation with age at diagnosis, reflecting clinical heterogeneity and outcome of neuroblastoma tumors.
Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome. Childhood neuroblastoma can be separated into high and low risk groups, with prognosis depending on age at diagnosis. Here, the authors show that low and high risk neuroblastoma tumours are composed of different cell types with different malignancy potential.
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