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Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions

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Item Type:Article
Title:Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions
Creators Name:Schmelz, K. and Toedling, J. and Huska, M. and Cwikla, M.C. and Kruetzfeldt, L.M. and Proba, J. and Ambros, P.F. and Ambros, I.M. and Boral, S. and Lodrini, M. and Chen, C.Y. and Burkert, M. and Guergen, D. and Szymansky, A. and Astrahantseff, K. and Kuenkele, A. and Haase, K. and Fischer, M. and Deubzer, H.E. and Hertwig, F. and Hundsdoerfer, P. and Henssen, A.G. and Schwarz, R.F. and Schulte, J.H. and Eggert, A.
Abstract:Intratumour heterogeneity is a major cause of treatment failure in cancer. We present in-depth analyses combining transcriptomic and genomic profiling with ultra-deep targeted sequencing of multiregional biopsies in 10 patients with neuroblastoma, a devastating childhood tumour. We observe high spatial and temporal heterogeneity in somatic mutations and somatic copy-number alterations which are reflected on the transcriptomic level. Mutations in some druggable target genes including ALK and FGFR1 are heterogeneous at diagnosis and/or relapse, raising the issue whether current target prioritization and molecular risk stratification procedures in single biopsies are sufficiently reliable for therapy decisions. The genetic heterogeneity in gene mutations and chromosome aberrations observed in deep analyses from patient courses suggest clonal evolution before treatment and under treatment pressure, and support early emergence of metastatic clones and ongoing chromosomal instability during disease evolution. We report continuous clonal evolution on mutational and copy number levels in neuroblastoma, and detail its implications for therapy selection, risk stratification and therapy resistance.
Keywords:Cancer Genetics, Cancer Genomics, CNS Cancer, Paediatric Cancer, Tumour Heterogeneity
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:12
Number:1
Page Range:6804
Date:23 November 2021
Official Publication:https://doi.org/10.1038/s41467-021-26870-z
PubMed:View item in PubMed

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