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{Lin:2019:10.1158/2159-8290.cd-18-0715,
author = {Lin, KK and Harrell, MI and Oza, AM and Oaknin, A and Ray-Coquard, I and Tinker, AV and Helman, E and Radke, MR and Say, C and Vo, L-T and Mann, E and Isaacson, JD and Maloney, L and O'Malley, DM and Chambers, SK and Kaufmann, SH and Scott, CL and Konecny, GE and Coleman, RL and Sun, JX and Giordano, H and Brenton, JD and Harding, TC and McNeish, IA and Swisher, EM},
doi = {10.1158/2159-8290.cd-18-0715},
journal = {Cancer Discovery},
pages = {210--219},
title = {BRCA reversion mutations in circulating tumor DNA predict primary and acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma},
url = {http://dx.doi.org/10.1158/2159-8290.cd-18-0715},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A key resistance mechanism to platinum-based chemotherapies and PARP inhibitors in BRCA-mutant cancers is the acquisition of BRCA reversion mutations that restore protein function. To estimate the prevalence of BRCA reversion mutations in high-grade ovarian carcinoma (HGOC), we performed targeted next-generation sequencing of circulating cell-free DNA (cfDNA) extracted from pretreatment and postprogression plasma in patients with deleterious germline or somatic BRCA mutations treated with the PARP inhibitor rucaparib. BRCA reversion mutations were identified in pretreatment cfDNA from 18% (2/11) of platinum-refractory and 13% (5/38) of platinum-resistant cancers, compared to 2% (1/48) of platinum-sensitive cancers (P = 0.049). Patients without BRCA reversion mutations detected in pretreatment cfDNA had significantly longer rucaparib progression-free survival than those with reversion mutations (median, 9.0 vs. 1.8 months; HR, 0.12; P < 0.0001). To study acquired resistance, we sequenced 78 postprogression cfDNA, identifying eight additional patients with BRCA reversion mutations not found in pretreatment cfDNA.
AU  - Lin,KK
AU  - Harrell,MI
AU  - Oza,AM
AU  - Oaknin,A
AU  - Ray-Coquard,I
AU  - Tinker,AV
AU  - Helman,E
AU  - Radke,MR
AU  - Say,C
AU  - Vo,L-T
AU  - Mann,E
AU  - Isaacson,JD
AU  - Maloney,L
AU  - O'Malley,DM
AU  - Chambers,SK
AU  - Kaufmann,SH
AU  - Scott,CL
AU  - Konecny,GE
AU  - Coleman,RL
AU  - Sun,JX
AU  - Giordano,H
AU  - Brenton,JD
AU  - Harding,TC
AU  - McNeish,IA
AU  - Swisher,EM
DO  - 10.1158/2159-8290.cd-18-0715
EP  - 219
PY  - 2019///
SN  - 2159-8274
SP  - 210
TI  - BRCA reversion mutations in circulating tumor DNA predict primary and acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma
T2  - Cancer Discovery
UR  - http://dx.doi.org/10.1158/2159-8290.cd-18-0715
UR  - http://hdl.handle.net/10044/1/64345
VL  - 9
ER  -
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