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Gain of chromosome 17 is an early genetic abnormality in neuroblastoma with PPM1D emerging as a strong candidate oncogene driving tumor progression

Milosevic, Jelena ; Fransson, Susanne ; Svensson, Johanna ; Otte, Jörg ; Olsen, Thale K. ; Sveinbjornsson, Baldur ; Hertwig, Falk ; Bartenhagen, Christoph ; Abel, Frida and Reinsbach, Susanne E. , et al. (2025) In Cancer Letters 625.
Abstract

Segmental gain of chromosome 17q is the most common genetic aberration in high-risk neuroblastoma, but its role in disease progression is poorly understood. This study aims to address the contribution of 17q gain to neuroblastoma malignancy. We analyzed the genetic and transcriptional landscape of 417 neuroblastoma patients across various risk groups and clinical stages using multi-omic approaches. Single-cell RNA/DNA sequencing and SNP arrays were combined to characterize genomic aberrations, while evolutionary trajectories were mapped to explore the accumulation of genetic changes in patients with neuroblastoma. Additionally, DNA and RNA sequencing were used to assess mutational burden and gene expression patterns. Our findings... (More)

Segmental gain of chromosome 17q is the most common genetic aberration in high-risk neuroblastoma, but its role in disease progression is poorly understood. This study aims to address the contribution of 17q gain to neuroblastoma malignancy. We analyzed the genetic and transcriptional landscape of 417 neuroblastoma patients across various risk groups and clinical stages using multi-omic approaches. Single-cell RNA/DNA sequencing and SNP arrays were combined to characterize genomic aberrations, while evolutionary trajectories were mapped to explore the accumulation of genetic changes in patients with neuroblastoma. Additionally, DNA and RNA sequencing were used to assess mutational burden and gene expression patterns. Our findings suggest that chromosome 17 gain is an early genetic event acquired during neuroblastoma development, correlating with the accumulation of additional chromosomal aberrations and poor prognosis. Increased segmental gains of chromosome 17q were observed during clonal evolution, relapse disease and metastasis. We identified PPM1D, a p53-inducible Ser/Thr phosphatase located on chr17q22.3, as a key player activated by segmental 17q-gain, gene-fusion, or gain-of-function somatic and germline mutations, further promoting neuroblastoma development/progression. Gain of chromosome 17 is an early driver of genetic instability in neuroblastoma, with PPM1D emerging as a potential candidate gene implicated in high-risk disease progression.

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type
Contribution to journal
publication status
published
subject
keywords
Chromosome 17q, Neuroblastoma, p53, PPM1D, WIP1
in
Cancer Letters
volume
625
article number
217769
publisher
Elsevier
external identifiers
  • pmid:40320038
  • scopus:105004693289
ISSN
0304-3835
DOI
10.1016/j.canlet.2025.217769
language
English
LU publication?
yes
id
80aeec02-df88-49cd-a5bb-e995f4c98af9
date added to LUP
2025-07-16 14:09:41
date last changed
2025-07-16 14:09:56
@article{80aeec02-df88-49cd-a5bb-e995f4c98af9,
  abstract     = {{<p>Segmental gain of chromosome 17q is the most common genetic aberration in high-risk neuroblastoma, but its role in disease progression is poorly understood. This study aims to address the contribution of 17q gain to neuroblastoma malignancy. We analyzed the genetic and transcriptional landscape of 417 neuroblastoma patients across various risk groups and clinical stages using multi-omic approaches. Single-cell RNA/DNA sequencing and SNP arrays were combined to characterize genomic aberrations, while evolutionary trajectories were mapped to explore the accumulation of genetic changes in patients with neuroblastoma. Additionally, DNA and RNA sequencing were used to assess mutational burden and gene expression patterns. Our findings suggest that chromosome 17 gain is an early genetic event acquired during neuroblastoma development, correlating with the accumulation of additional chromosomal aberrations and poor prognosis. Increased segmental gains of chromosome 17q were observed during clonal evolution, relapse disease and metastasis. We identified PPM1D, a p53-inducible Ser/Thr phosphatase located on chr17q22.3, as a key player activated by segmental 17q-gain, gene-fusion, or gain-of-function somatic and germline mutations, further promoting neuroblastoma development/progression. Gain of chromosome 17 is an early driver of genetic instability in neuroblastoma, with PPM1D emerging as a potential candidate gene implicated in high-risk disease progression.</p>}},
  author       = {{Milosevic, Jelena and Fransson, Susanne and Svensson, Johanna and Otte, Jörg and Olsen, Thale K. and Sveinbjornsson, Baldur and Hertwig, Falk and Bartenhagen, Christoph and Abel, Frida and Reinsbach, Susanne E. and Djos, Anna and Javanmardi, Niloufar and Shi, Yao and Hehir-Kwa, Jane Y. and Mensenkamp, Arjen and Tytgat, Godelieve AM and Holmberg, Johan and Molenaar, Jan J. and Jongmans, Marjolijn and Fischer, Matthias and Baryawno, Ninib and Gisselsson, David and Martinsson, Tommy and Kogner, Per and Johnsen, John Inge}},
  issn         = {{0304-3835}},
  keywords     = {{Chromosome 17q; Neuroblastoma; p53; PPM1D; WIP1}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Elsevier}},
  series       = {{Cancer Letters}},
  title        = {{Gain of chromosome 17 is an early genetic abnormality in neuroblastoma with PPM1D emerging as a strong candidate oncogene driving tumor progression}},
  url          = {{http://dx.doi.org/10.1016/j.canlet.2025.217769}},
  doi          = {{10.1016/j.canlet.2025.217769}},
  volume       = {{625}},
  year         = {{2025}},
}