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Cancer evolution, mutations, and clonal selection in relapse neuroblastoma

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Molecular Oncology, Internal Medicine/Cancer Research Unit, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany

    Marc Schulte & Alexander Schramm

  2. Genome Informatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Johannes Köster & Sven Rahmann

  3. Computer Science, TU Dortmund, Dortmund, Germany

    Sven Rahmann

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  1. Marc Schulte
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Correspondence to Marc Schulte.

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Schulte, M., Köster, J., Rahmann, S. et al. Cancer evolution, mutations, and clonal selection in relapse neuroblastoma. Cell Tissue Res 372, 263–268 (2018). https://doi.org/10.1007/s00441-018-2810-5

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