Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma

Jenny Karlsson, Hiroaki Yasui, Adriana Mañas, Natalie Andersson, Karin Hansson, Kristina Aaltonen, Caroline Jansson, Geoffroy Durand, Naveen Ravi, Michele Ferro, Minjun Yang, Subhayan Chattopadhyay, Kajsa Paulsson, Diana Spierings, Floris Foijer, Anders Valind, Daniel Bexell and David Gisselsson ()
Additional contact information
Jenny Karlsson: Lund University
Hiroaki Yasui: Lund University
Adriana Mañas: Lund University
Natalie Andersson: Lund University
Karin Hansson: Lund University
Kristina Aaltonen: Lund University
Caroline Jansson: Lund University
Geoffroy Durand: Lund University
Naveen Ravi: Lund University
Michele Ferro: Lund University
Minjun Yang: Lund University
Subhayan Chattopadhyay: Lund University
Kajsa Paulsson: Lund University
Diana Spierings: University Medical Center Groningen
Floris Foijer: University Medical Center Groningen
Anders Valind: Lund University
Daniel Bexell: Lund University
David Gisselsson: Lund University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Neuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. 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 replicate these two contrasting scenarios and show 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53334-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53334-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53334-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().