Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Title: Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.
Authors: Cooper, CS
Eeles, R
Wedge, DC
Van Loo, P
Gundem, G
Alexandrov, LB
Kremeyer, B
Butler, A
Lynch, AG
Camacho, N
Massie, CE
Kay, J
Luxton, HJ
Edwards, S
Kote-Jarai, Z
Dennis, N
Merson, S
Leongamornlert, D
Zamora, J
Corbishley, C
Thomas, S
Nik-Zainal, S
Ramakrishna, M
O'Meara, S
Matthews, L
Clark, J
Hurst, R
Mithen, R
Bristow, RG
Boutros, PC
Fraser, M
Cooke, S
Raine, K
Jones, D
Menzies, A
Stebbings, L
Hinton, J
Teague, J
McLaren, S
Mudie, L
Hardy, C
Anderson, E
Joseph, O
Goody, V
Robinson, B
Maddison, M
Gamble, S
Greenman, C
Berney, D
Hazell, S
Livni, N
ICGC Prostate Group,
Fisher, C
Ogden, C
Kumar, P
Thompson, A
Woodhouse, C
Nicol, D
Mayer, E
Dudderidge, T
Shah, NC
Gnanapragasam, V
Voet, T
Campbell, P
Futreal, A
Easton, D
Warren, AY
Foster, CS
Stratton, MR
Whitaker, HC
McDermott, U
Brewer, DS
Neal, DE
Item Type: Journal Article
Abstract: © 2015 Nature America, Inc. All rights reserved.Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.
Issue Date: 2-Mar-2015
Date of Acceptance: 21-Jan-2015
URI: http://hdl.handle.net/10044/1/27635
DOI: https://dx.doi.org/10.1038/ng.3221
ISSN: 1546-1718
Publisher: Nature Publishing Group
Start Page: 367
End Page: 372
Journal / Book Title: Nature Genetics
Volume: 47
Issue: 4
Copyright Statement: © 2015, Rights Managed by Nature Publishing Group
Keywords: Case-Control Studies
Cell Lineage
Clonal Evolution
Clone Cells
DNA Mutational Analysis
Humans
Male
Mutation
Neoplasms, Multiple Primary
Phylogeny
Prostate
Prostatic Neoplasms
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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