guest ::
| Home > Publications database > Micronuclear ecDNA constrains tumor cell fitness and is associated with favorable patient survival. |
| Home > Publications database > Micronuclear ecDNA constrains tumor cell fitness and is associated with favorable patient survival. |
| Journal Article | DKFZ-2026-02506 |
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
2026
Macmillan Publishers Limited, part of Springer Nature
London
Abstract: Extrachromosomal DNA (ecDNA) contributes to cancer genome instability by enabling high-copy oncogene amplification and genetic intratumoral heterogeneity. Micronuclei (MNs) are common in chromosomally unstable cancers, yet their role in ecDNA-driven tumors remains unclear. Here we investigate how ecDNA damage, mitotic segregation and MN formation are linked. We find that ecDNAs are a major source of MNs following their damage, particularly under replication stress. Replication stress promotes mitotic ecDNA clustering, asymmetric inheritance, mis-segregation into MNs and reduced transcriptional output. Single-MN sequencing reveals that multiple distinct ecDNA species coalesce within individual MNs. Cells inheriting ecDNA+ MNs display impaired proliferative capacity and are more likely to undergo cell death. In patients with MYCN-amplified neuroblastoma, higher frequencies of ecDNA+ MNs at diagnosis are associated with improved overall survival. Together, these findings identify ecDNA mis-segregation as a mechanism that limits tumor fitness, highlighting mitotic ecDNA retention as a potential therapeutic vulnerability.
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
