Academic Journal
Mutational topography reflects clinical neuroblastoma heterogeneity
| Title: | Mutational topography reflects clinical neuroblastoma heterogeneity |
|---|---|
| Authors: | Elias Rodriguez-Fos, Mercè Planas-Fèlix, Martin Burkert, Montserrat Puiggròs, Joern Toedling, Nina Thiessen, Eric Blanc, Annabell Szymansky, Falk Hertwig, Naveed Ishaque, Dieter Beule, David Torrents, Angelika Eggert, Richard P. Koche, Roland F. Schwarz, Kerstin Haase, Johannes H. Schulte, Anton G. Henssen |
| Source: | Cell Genomics, Vol 3, Iss 10, Pp 100402- (2023) |
| Publisher Information: | Elsevier, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Genetics LCC:Internal medicine |
| Subject Terms: | neuroblastoma, mutational signatures, cancer genomics, tumor evolution, ecDNA, complex rearrangements, Genetics, QH426-470, Internal medicine, RC31-1245 |
| More Details: | Summary: Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although clinical risk-defining genomic alterations exist in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography and mutational signatures derived from all variant classes, we identified co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is associated with differences in the mutational processes driving these scenarios, linking risk-defining pathognomonic variants to distinct molecular processes. Whereas high-risk MYCN-amplified neuroblastomas were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas were marked by footprints of chromosome mis-segregation and TOP1 mutational activity. Furthermore, analysis of subclonal mutations uncovered differential activity of these processes through neuroblastoma evolution. Thus, clinical heterogeneity of neuroblastoma patients can be linked to differences in the mutational processes that are active in their tumors. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2666-979X |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2666979X23002161; https://doaj.org/toc/2666-979X |
| DOI: | 10.1016/j.xgen.2023.100402 |
| Access URL: | https://doaj.org/article/0df526825af642e280ef874891c577b1 |
| Accession Number: | edsdoj.0df526825af642e280ef874891c577b1 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2666979X |
|---|---|
| DOI: | 10.1016/j.xgen.2023.100402 |
| Published in: | Cell Genomics |
| Language: | English |