Genomics

Dataset Information

0

Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma


ABSTRACT: Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.

PROVIDER: EGAS00001007650 | EGA |

REPOSITORIES: EGA

Similar Datasets

2013-02-13 | E-GEOD-37469 | biostudies-arrayexpress
2022-11-12 | E-MTAB-12238 | biostudies-arrayexpress
2013-02-13 | GSE37469 | GEO
2024-01-26 | PXD042422 | Pride
2023-02-05 | GSE212645 | GEO
2016-03-01 | E-GEOD-74622 | biostudies-arrayexpress
2016-03-01 | GSE74622 | GEO
2012-10-01 | GSE39641 | GEO
2018-07-05 | PXD005864 | Pride
2014-06-17 | MTBLS92 | MetaboLights