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BibTex format

@article{McNeish:2025:10.1038/s41467-025-60655-y,
author = {McNeish, I and Ewing, A and Meynert, A and Silk, R and Aitken, S and Bendixsen, DP and Churchman, M and Brown, SL and Hamdan, A and Mattocks, J and Grimes, GR and Ballinger, T and Hollis, RL and Herrington, CS and Thomson, JP and Sherwood, K and Parry, T and Esiri-Bloom, E and Bartos, C and Croy, I and Ferguson, M and Lennie, M and McGoldrick, T and McPhail, N and Siddiqui, N and Glasspool, R and Mackean, M and Nussey, F and McDade, B and Ennis, D and McMahon, L and Matakidou, A and Dougherty, B and March, R and Barrett, JC and McNeish, IA and Biankin, AV and Roxburgh, P and Gourley, C and Semple, CA},
doi = {10.1038/s41467-025-60655-y},
journal = {Nature Communications},
title = {Divergent trajectories to structural diversity impact patient survival in high grade serous ovarian cancer},
url = {http://dx.doi.org/10.1038/s41467-025-60655-y},
volume = {16},
year = {2025}
}
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TY  - JOUR
AB  - Deciphering the structural variation across tumour genomes is crucial to determine the events driving tumour progression and better understand tumour adaptation and evolution. High grade serous ovarian cancer (HGSOC) is an exemplar tumour type showing extreme, but poorly characterised structural diversity. Here, we comprehensively describe the mutational landscape driving HGSOC, exploiting a large (N=324), deeply whole genome sequenced dataset. We reveal two divergent evolutionary trajectories, affecting patient survival and involving differing genomic environments. One involves homologous recombination repair deficiency (HRD) while the other is dominated by whole genome duplication (WGD) with frequent chromothripsis, breakage-fusion-bridges and extra-chromosomal DNA. These trajectories contribute to structural variation hotspots, containing candidate driver genes with significantly altered expression. While structural variation predominantly drives tumorigenesis, we find high mtDNA mutation loads associated with shorter patient survival. We show that a combination of mutations in the mitochondrial and nuclear genomes impact prognosis, suggesting strategies for patient stratification.
AU  - McNeish,I
AU  - Ewing,A
AU  - Meynert,A
AU  - Silk,R
AU  - Aitken,S
AU  - Bendixsen,DP
AU  - Churchman,M
AU  - Brown,SL
AU  - Hamdan,A
AU  - Mattocks,J
AU  - Grimes,GR
AU  - Ballinger,T
AU  - Hollis,RL
AU  - Herrington,CS
AU  - Thomson,JP
AU  - Sherwood,K
AU  - Parry,T
AU  - Esiri-Bloom,E
AU  - Bartos,C
AU  - Croy,I
AU  - Ferguson,M
AU  - Lennie,M
AU  - McGoldrick,T
AU  - McPhail,N
AU  - Siddiqui,N
AU  - Glasspool,R
AU  - Mackean,M
AU  - Nussey,F
AU  - McDade,B
AU  - Ennis,D
AU  - McMahon,L
AU  - Matakidou,A
AU  - Dougherty,B
AU  - March,R
AU  - Barrett,JC
AU  - McNeish,IA
AU  - Biankin,AV
AU  - Roxburgh,P
AU  - Gourley,C
AU  - Semple,CA
DO  - 10.1038/s41467-025-60655-y
PY  - 2025///
SN  - 2041-1723
TI  - Divergent trajectories to structural diversity impact patient survival in high grade serous ovarian cancer
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-025-60655-y
VL  - 16
ER  -
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