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Tracing metastatic spread in pediatric solid tumors using copy number and targeted deep sequencing.

Natalie Andersson1,2,3, Michele Ferro1, Caroline Jansson1

  • 1Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.

The Journal of Pathology
|September 23, 2025
PubMed
Summary

Pediatric cancer metastasis is poorly understood. This study reveals that metastases can arise early in tumor development and spread multiple times, even between metastatic sites, challenging current treatment paradigms.

Keywords:
SNP‐arrayWilms tumorcancer evolutioncopy number alterationsgonadal tumorsmutationsneuroblastomaphylogeneticstargeted deep sequencing

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Area of Science:

  • Pediatric Oncology
  • Cancer Metastasis Research
  • Genomic Profiling

Background:

  • Treatment-resistant tumors and metastasis are leading causes of death in pediatric cancer.
  • Mechanisms of metastatic spread in pediatric tumors are largely unknown.

Purpose of the Study:

  • To investigate the spatiotemporal evolution of pediatric tumors and their metastatic spread.
  • To identify early metastatic events and intermetastatic dissemination patterns.

Main Methods:

  • Whole-genome copy number profiling of primary tumors and metastases from 17 pediatric cancer patients.
  • Targeted deep sequencing and phylogenetic reconstruction for subclone tracking.

Main Results:

  • 11 of 17 patients showed metastases arising before the primary tumor's common ancestor.
  • Multiple metastatic events from different subclones occurred in 8 patients.
  • Intermetastatic spread was observed in 8 of 9 patients with multiple metastatic sites.

Conclusions:

  • Metastatic spread in pediatric cancers is a complex, multi-stage process.
  • Early dissemination and intermetastatic spread are common, impacting treatment strategies.
  • Understanding these mechanisms is crucial for developing effective pediatric cancer therapies.