Imperial College London
Alternate

ProfessorGeorgeHanna

Faculty of Medicine, Department of Surgery & Cancer

Head of Department of Surgery and Cancer
 
 
 
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Contact

 

+44 (0)20 7594 3396g.hanna

 
 
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Assistant

 

Ms Aoibheann Byrne +44 (0)20 7594 3396

 
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Location

 

Block B Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mourikis:2019:10.1038/s41467-019-10898-3,
author = {Mourikis, TP and Benedetti, L and Foxall, E and Temelkovski, D and Nulsen, J and Perner, J and Cereda, M and Lagergren, J and Howell, M and Yau, C and Fitzgerald, RC and Scaffidi, P and Noorani, A and Edwards, PAW and Elliott, RF and Grehan, N and Nutzinger, B and Hughes, C and Fidziukiewicz, E and Bornschein, J and MacRae, S and Crawte, J and Northrop, A and Contino, G and Li, X and de, la Rue R and Katz-Summercorn, A and Abbas, S and Loureda, D and O'Donovan, M and Miremadi, A and Malhotra, S and Tripathi, M and Tavare, S and Lynch, AG and Eldridge, M and Secrier, M and Bower, L and Devonshire, G and Jammula, S and Davies, J and Crichton, C and Carroll, N and Safranek, P and Hindmarsh, A and Sujendran, V and Hayes, SJ and Ang, Y and Sharrocks, A and Preston, SR and Oakes, S and Bagwan, I and Save, V and Skipworth, RJE and Hupp, TR and O'Neill, JR and Tucker, O and Beggs, A and Taniere, P and Puig, S and Underwood, TJ and Walker, RC and Grace, BL and Barr, H and Shepherd, N and Old, O},
doi = {10.1038/s41467-019-10898-3},
journal = {Nature Communications},
pages = {1--17},
title = {Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma},
url = {http://dx.doi.org/10.1038/s41467-019-10898-3},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
AU  - Mourikis,TP
AU  - Benedetti,L
AU  - Foxall,E
AU  - Temelkovski,D
AU  - Nulsen,J
AU  - Perner,J
AU  - Cereda,M
AU  - Lagergren,J
AU  - Howell,M
AU  - Yau,C
AU  - Fitzgerald,RC
AU  - Scaffidi,P
AU  - Noorani,A
AU  - Edwards,PAW
AU  - Elliott,RF
AU  - Grehan,N
AU  - Nutzinger,B
AU  - Hughes,C
AU  - Fidziukiewicz,E
AU  - Bornschein,J
AU  - MacRae,S
AU  - Crawte,J
AU  - Northrop,A
AU  - Contino,G
AU  - Li,X
AU  - de,la Rue R
AU  - Katz-Summercorn,A
AU  - Abbas,S
AU  - Loureda,D
AU  - O'Donovan,M
AU  - Miremadi,A
AU  - Malhotra,S
AU  - Tripathi,M
AU  - Tavare,S
AU  - Lynch,AG
AU  - Eldridge,M
AU  - Secrier,M
AU  - Bower,L
AU  - Devonshire,G
AU  - Jammula,S
AU  - Davies,J
AU  - Crichton,C
AU  - Carroll,N
AU  - Safranek,P
AU  - Hindmarsh,A
AU  - Sujendran,V
AU  - Hayes,SJ
AU  - Ang,Y
AU  - Sharrocks,A
AU  - Preston,SR
AU  - Oakes,S
AU  - Bagwan,I
AU  - Save,V
AU  - Skipworth,RJE
AU  - Hupp,TR
AU  - O'Neill,JR
AU  - Tucker,O
AU  - Beggs,A
AU  - Taniere,P
AU  - Puig,S
AU  - Underwood,TJ
AU  - Walker,RC
AU  - Grace,BL
AU  - Barr,H
AU  - Shepherd,N
AU  - Old,O
AU  - Gossage,J
AU  - Davies,A
AU  - Chang,F
AU  - Zylstra,J
AU  - Mahadeva,U
AU  - Goh,V
AU  - Sanders,G
AU  - Berrisford,R
AU  - Harden,C
AU  - Lewis,M
AU  - Cheong,E
AU  - Kumar,B
AU  - Parsons,SL
AU  - Soomro,I
AU  - Kaye,P
AU  - Saunders,J
AU  - Lovat,L
AU  - Haidry,R
AU  - Igali,L
AU  - Scott,M
AU  - Sothi,S
AU  - Suortamo,S
AU  - Lishman,S
AU  - Hanna,GB
AU  - Peters,CJ
AU  - Moorthy,K
AU  - Grabowska,A
AU  - Turkington,R
AU  - McManus,D
AU  - Khoo,D
AU  - Fickling,W
AU  - Ciccarelli,FD
DO  - 10.1038/s41467-019-10898-3
EP  - 17
PY  - 2019///
SN  - 2041-1723
SP  - 1
TI  - Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-019-10898-3
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000475469200005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41467-019-10898-3
UR  - http://hdl.handle.net/10044/1/72482
VL  - 10
ER  -
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