Cell and Tissue Research

, Volume 372, Issue 2, pp 263–268 | Cite as

Cancer evolution, mutations, and clonal selection in relapse neuroblastoma

  • Marc SchulteEmail author
  • Johannes Köster
  • Sven Rahmann
  • Alexander Schramm


The notion of cancer as a complex evolutionary system has been validated by in-depth molecular analyses of tumor progression over the last years. While a complex interplay of cell-autonomous programs and cell-cell interactions determines proliferation and differentiation during normal development, intrinsic and acquired plasticity of cancer cells allow for evasion of growth factor limitations, apoptotic signals, or attacks from the immune system. Treatment-induced molecular selection processes have been described by a number of studies already, but understanding of those events facilitating metastatic spread, organ-specific homing, and resistance to anoikis is still in its early days. In principle, somatic events giving rise to cancer progression should be easier to follow in childhood tumors bearing fewer mutations and genomic aberrations than their counterparts in adulthood. We have previously reported on the genetic events accompanying relapsing neuroblastoma, a solid tumor of early childhood. Our results indicated significantly higher single nucleotide variants in relapse tumors, gave hints for branched tumor evolution upon treatment and clonal selection as deduced from shifts in allelic frequencies between primary and relapsing neuroblastoma. Here, we will review these findings and give an outlook on dealing with intratumoral heterogeneity and sub-clonal diversity in neuroblastoma for future targeted treatments.


Neuroblastoma Clonal selection Intratumoral heterogeneity Pediatric Relapse 



Work of AS and SR is supported by the DFG within Collaborative Research Center SFB876, TP C1 and the BMBF as part of the program “SYSMED-NB”, TP A2 and B3.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Molecular Oncology, Internal Medicine/Cancer Research UnitUniversity Hospital Essen, University of Duisburg-EssenEssenGermany
  2. 2.Genome Informatics, Institute of Human GeneticsUniversity Hospital Essen, University of Duisburg-EssenEssenGermany
  3. 3.Computer Science, TU DortmundDortmundGermany

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