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

Karlsson, Jenny LU ; Yasui, Hiroaki LU ; Manas Nunez, Adriana LU ; Andersson, Natalie LU orcid ; Hansson, Karin LU orcid ; Aaltonen, Kristina LU orcid ; Jansson, Caroline LU ; Durand, Geoffroy LU ; Ravi, Naveen LU and Ferro, Michele LU , et al. (2024) In Nature Communications 15(1).
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
15
issue
1
article number
8992
publisher
Nature Publishing Group
external identifiers
  • pmid:39419962
  • scopus:85206640039
ISSN
2041-1723
DOI
10.1038/s41467-024-53334-x
language
English
LU publication?
yes
id
f87aade7-fc6a-4288-ac5c-e10e26f4e09c
date added to LUP
2024-10-20 09:51:16
date last changed
2025-04-04 13:58:27
@article{f87aade7-fc6a-4288-ac5c-e10e26f4e09c,
  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.}},
  author       = {{Karlsson, Jenny and Yasui, Hiroaki and Manas Nunez, Adriana and Andersson, Natalie and Hansson, Karin and Aaltonen, Kristina and Jansson, Caroline and Durand, Geoffroy and Ravi, Naveen and Ferro, Michele and Yang, Minjun and Chattopadhyay, Subhayan and Paulsson, Kajsa and Spierings, Diana C J and Foijer, Floris and Valind, Anders and Bexell, Daniel and Gisselsson Nord, David}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-53334-x}},
  doi          = {{10.1038/s41467-024-53334-x}},
  volume       = {{15}},
  year         = {{2024}},
}