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{Martins:2022:10.1038/s41467-022-33870-0,
author = {Martins, FC and Couturier, D-L and de, Santiago I and Sauer, CM and Vias, M and Angelova, M and Sanders, D and Piskorz, A and Hall, J and Hosking, K and Amirthanayagam, A and Cosulich, S and Carnevalli, L and Davies, B and Watkins, TBK and Funingana, IG and Bolton, H and Haldar, K and Latimer, J and Baldwin, P and Crawford, R and Eldridge, M and Basu, B and Jimenez-Linan, M and Mcpherson, AW and McGranahan, N and Litchfield, K and Shah, SP and McNeish, I and Caldas, C and Evan, G and Swanton, C and Brenton, JD},
doi = {10.1038/s41467-022-33870-0},
journal = {Nature Communications},
title = {Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer},
url = {http://dx.doi.org/10.1038/s41467-022-33870-0},
volume = {13},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identify five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reason that their strong selection should prioritise them as key biomarkers for targeted therapies. We use primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number is associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC is statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway is independently observed in squamous lung cancer and triple negative breast cancer. In this work, we show that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.
AU  - Martins,FC
AU  - Couturier,D-L
AU  - de,Santiago I
AU  - Sauer,CM
AU  - Vias,M
AU  - Angelova,M
AU  - Sanders,D
AU  - Piskorz,A
AU  - Hall,J
AU  - Hosking,K
AU  - Amirthanayagam,A
AU  - Cosulich,S
AU  - Carnevalli,L
AU  - Davies,B
AU  - Watkins,TBK
AU  - Funingana,IG
AU  - Bolton,H
AU  - Haldar,K
AU  - Latimer,J
AU  - Baldwin,P
AU  - Crawford,R
AU  - Eldridge,M
AU  - Basu,B
AU  - Jimenez-Linan,M
AU  - Mcpherson,AW
AU  - McGranahan,N
AU  - Litchfield,K
AU  - Shah,SP
AU  - McNeish,I
AU  - Caldas,C
AU  - Evan,G
AU  - Swanton,C
AU  - Brenton,JD
DO  - 10.1038/s41467-022-33870-0
PY  - 2022///
SN  - 2041-1723
TI  - Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-022-33870-0
UR  - http://hdl.handle.net/10044/1/100420
VL  - 13
ER  -
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