dc.contributor.author
Schmelz, Karin
dc.contributor.author
Toedling, Joern
dc.contributor.author
Huska, Matt
dc.contributor.author
Cwikla, Maja C.
dc.contributor.author
Kruetzfeldt, Louisa-Marie
dc.contributor.author
Proba, Jutta
dc.contributor.author
Ambros, Peter F.
dc.contributor.author
Ambros, Inge M.
dc.contributor.author
Boral, Sengül
dc.contributor.author
Lodrini, Marco
dc.contributor.author
Chen, Celine Y.
dc.contributor.author
Burkert, Martin
dc.contributor.author
Guergen, Dennis
dc.contributor.author
Szymansky, Annabell
dc.contributor.author
Astrahantseff, Kathy
dc.contributor.author
Kuenkele, Annette
dc.contributor.author
Haase, Kerstin
dc.contributor.author
Fischer, Matthias
dc.contributor.author
Deubzer, Hedwig E.
dc.contributor.author
Hertwig, Falk
dc.contributor.author
Hundsdoerfer, Patrick
dc.contributor.author
Henssen, Anton G.
dc.contributor.author
Schwarz, Roland F.
dc.contributor.author
Schulte, Johannes H.
dc.contributor.author
Eggert, Angelika
dc.date.accessioned
2023-03-09T15:47:54Z
dc.date.available
2023-03-09T15:47:54Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/38262
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-37981
dc.description.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.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
intratumour heterogeneity
en
dc.subject
neuroblastoma
en
dc.subject
multiregional biopsies
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
6804
dcterms.bibliographicCitation.doi
10.1038/s41467-021-26870-z
dcterms.bibliographicCitation.journaltitle
Nature Communications
dcterms.bibliographicCitation.originalpublishername
Springer Nature
dcterms.bibliographicCitation.volume
12
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
Springer Nature DEAL
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34815394
dcterms.isPartOf.eissn
2041-1723