Imperial College London
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ProfessorIainMcNeish

Faculty of Medicine, Department of Surgery & Cancer

Chair in Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2185i.mcneish Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

G036Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cheng:2022:10.1158/1078-0432.CCR-21-1643,
author = {Cheng, Z and Mirza, H and Ennis, DP and Smith, P and Morrill, Gavarro L and Sokota, C and Giannone, G and Goranova, T and Bradley, T and Piskorz, A and Lockley, M and for, the BriTROC-1 Investigators and Kaur, B and Singh, N and Tookman, L and Krell, J and McDermott, J and Macintyre, G and Markowetz, F and Brenton, JD and McNeish, I},
doi = {10.1158/1078-0432.CCR-21-1643},
journal = {Clinical Cancer Research},
pages = {2911--2922},
title = {The genomic landscape of early-stage ovarian high grade serous carcinoma},
url = {http://dx.doi.org/10.1158/1078-0432.CCR-21-1643},
volume = {28},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Purpose: Ovarian high grade serous carcinoma (HGSC) is usually diagnosed at late stage. We investigated whether late-stage HGSC has unique genomic characteristics consistent with acquisition of volutionary advantage compared to early-stage tumours.Experimental Design: We performed targeted next generation sequencing and shallow whole genome sequencing (sWGS) on pre-treatment samples from 43 patients with FIGO stage I–IIA HGSC to investigate somatic mutations and copy number alterations (SCNA). We comparedresults to pre-treatment samples from 52 stage IIIC/IV HGSC patients from the BriTROC-1 study.Results: Age of diagnosis did not differ between early-stage and late-stage patients (median 61.3 years vs 62.3 years respectively). TP53 mutations were near-universal in both cohorts (89% early-stage, 100% late-stage) and there were no significant differences in the rates of other somatic mutations, including BRCA1 and BRCA2. We also did not observe cohort-specific focal SCNA that could explain biological behaviour. However, ploidy was higher in late-stage (median 3.0) than early-stage (median 1.9) samples. Copy number (CN) signature exposures were significantly different between cohorts, with greater relative signature 3 exposure in early-stage and greater signature 4 in late-stage. Unsupervised clustering based on CN signatures identified three clustersthat were prognostic.Conclusions: Early stage and late stage HGSC have highly similar patterns of mutation and focal SCNA. However, copy number signature analysis showed that late-stage disease has distinct signature exposures consistent with whole genome duplication. Further analyses will be required to ascertain whether these differences reflect genuine biological differences between early and late-stage or simply time-related markers of evolutionary fitness.
AU  - Cheng,Z
AU  - Mirza,H
AU  - Ennis,DP
AU  - Smith,P
AU  - Morrill,Gavarro L
AU  - Sokota,C
AU  - Giannone,G
AU  - Goranova,T
AU  - Bradley,T
AU  - Piskorz,A
AU  - Lockley,M
AU  - for,the BriTROC-1 Investigators
AU  - Kaur,B
AU  - Singh,N
AU  - Tookman,L
AU  - Krell,J
AU  - McDermott,J
AU  - Macintyre,G
AU  - Markowetz,F
AU  - Brenton,JD
AU  - McNeish,I
DO  - 10.1158/1078-0432.CCR-21-1643
EP  - 2922
PY  - 2022///
SN  - 1078-0432
SP  - 2911
TI  - The genomic landscape of early-stage ovarian high grade serous carcinoma
T2  - Clinical Cancer Research
UR  - http://dx.doi.org/10.1158/1078-0432.CCR-21-1643
UR  - https://aacrjournals.org/clincancerres/article/28/13/2911/704990/The-Genomic-Landscape-of-Early-Stage-Ovarian-High
UR  - http://hdl.handle.net/10044/1/94880
VL  - 28
ER  -
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