Imperial College London
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Erik Mayer

Faculty of Medicine, Department of Surgery & Cancer

Clinical Reader in Urology
 
 
 
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Contact

 

e.mayer Website

 
 
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Location

 

1020Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Camacho:2017:10.1371/journal.pgen.1007001,
author = {Camacho, N and Van, Loo P and Edwards, S and Kay, JD and Matthews, L and Haase, K and Clark, J and Dennis, N and Thomas, S and Kremeyer, B and Zamora, J and Butler, AP and Gundem, G and Merson, S and Luxton, H and Hawkins, S and Ghori, M and Marsden, L and Lambert, A and Karaszi, K and Pelvender, G and Massie, CE and Kote-Jarai, Z and Raine, K and Jones, D and Howat, WJ and Hazell, S and Livni, N and Fisher, C and Ogden, C and Kumar, P and Thompson, A and Nicol, D and Mayer, E and Dudderidge, T and Yu, Y and Zhang, H and Shah, NC and Gnanapragasam, VJ and CRUK-ICGC, Prostate Group and Isaacs, W and Visakorpi, T and Hamdy, F and Berney, D and Verrill, C and Warren, AY and Wedge, DC and Lynch, AG and Foster, CS and Lu, YJ and Bova, GS and Whitaker, HC and McDermott, U and Neal, DE and Eeles, R and Cooper, CS and Brewer, DS},
doi = {10.1371/journal.pgen.1007001},
journal = {PLoS Genetics},
title = {Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data},
url = {http://dx.doi.org/10.1371/journal.pgen.1007001},
volume = {13},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses.
AU  - Camacho,N
AU  - Van,Loo P
AU  - Edwards,S
AU  - Kay,JD
AU  - Matthews,L
AU  - Haase,K
AU  - Clark,J
AU  - Dennis,N
AU  - Thomas,S
AU  - Kremeyer,B
AU  - Zamora,J
AU  - Butler,AP
AU  - Gundem,G
AU  - Merson,S
AU  - Luxton,H
AU  - Hawkins,S
AU  - Ghori,M
AU  - Marsden,L
AU  - Lambert,A
AU  - Karaszi,K
AU  - Pelvender,G
AU  - Massie,CE
AU  - Kote-Jarai,Z
AU  - Raine,K
AU  - Jones,D
AU  - Howat,WJ
AU  - Hazell,S
AU  - Livni,N
AU  - Fisher,C
AU  - Ogden,C
AU  - Kumar,P
AU  - Thompson,A
AU  - Nicol,D
AU  - Mayer,E
AU  - Dudderidge,T
AU  - Yu,Y
AU  - Zhang,H
AU  - Shah,NC
AU  - Gnanapragasam,VJ
AU  - CRUK-ICGC,Prostate Group
AU  - Isaacs,W
AU  - Visakorpi,T
AU  - Hamdy,F
AU  - Berney,D
AU  - Verrill,C
AU  - Warren,AY
AU  - Wedge,DC
AU  - Lynch,AG
AU  - Foster,CS
AU  - Lu,YJ
AU  - Bova,GS
AU  - Whitaker,HC
AU  - McDermott,U
AU  - Neal,DE
AU  - Eeles,R
AU  - Cooper,CS
AU  - Brewer,DS
DO  - 10.1371/journal.pgen.1007001
PY  - 2017///
SN  - 1553-7390
TI  - Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data
T2  - PLoS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1007001
UR  - https://www.ncbi.nlm.nih.gov/pubmed/28945760
UR  - http://hdl.handle.net/10044/1/57967
VL  - 13
ER  -
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