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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/31972
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dc.contributor.authorEsentürk, E-
dc.contributor.authorSahli, A-
dc.contributor.authorHaberland, V-
dc.contributor.authorZiuboniewicz, A-
dc.contributor.authorWirth, C-
dc.contributor.authorBova, GS-
dc.contributor.authorBristow, RG-
dc.contributor.authorBrook, MN-
dc.contributor.authorBrors, B-
dc.contributor.authorButler, A-
dc.contributor.authorCancel-Tassin, G-
dc.contributor.authorCheng, KCL-
dc.contributor.authorCooper, CS-
dc.contributor.authorCorcoran, NM-
dc.contributor.authorCussenot, O-
dc.contributor.authorEeles, RA-
dc.contributor.authorFavero, F-
dc.contributor.authorGerhauser, C-
dc.contributor.authorGihawi, A-
dc.contributor.authorGirma, EG-
dc.contributor.authorGnanapragasam, VJ-
dc.contributor.authorGruber, AJ-
dc.contributor.authorHamid, A-
dc.contributor.authorHayes, VM-
dc.contributor.authorHe, HH-
dc.contributor.authorHovens, CM-
dc.contributor.authorImada, EL-
dc.contributor.authorJakobsdottir, GM-
dc.contributor.authorJung, C-H-
dc.contributor.authorKhani, F-
dc.contributor.authorKote-Jarai, Z-
dc.contributor.authorLamy, P-
dc.contributor.authorLeeman, G-
dc.contributor.authorLoda, M-
dc.contributor.authorLutsik, P-
dc.contributor.authorMarchionni, L-
dc.contributor.authorMolania, R-
dc.contributor.authorPapenfuss, AT-
dc.contributor.authorPellegrina, D-
dc.contributor.authorPope, B-
dc.contributor.authorQueiroz, LR-
dc.contributor.authorRausch, T-
dc.contributor.authorReimand, J-
dc.contributor.authorRobinson, B-
dc.contributor.authorSchlomm, T-
dc.contributor.authorSørensen, KD-
dc.contributor.authorUhrig, S-
dc.contributor.authorWeischenfeldt, J-
dc.contributor.authorXu, Y-
dc.contributor.authorYamaguchi, TN-
dc.contributor.authorZanettini, C-
dc.contributor.authorLynch, AG-
dc.contributor.authorWedge, DC-
dc.contributor.authorBrewer, DS-
dc.contributor.authorWoodcock, DJ-
dc.date.accessioned2025-09-10T15:12:11Z-
dc.date.available2025-09-10T15:12:11Z-
dc.date.issued2025-03-17-
dc.identifierORCiD: Valeriia Haberland https://orcid.org/0000-0002-3874-0683-
dc.identifierarXiv:2503.13189v1 [q-bio.GN]-
dc.identifier.citationEsentürk, E. et al. (2025) 'Causes of evolutionary divergence in prostate cancer', arXiv preprint, arXiv:2503.13189v1 [q-bio.GN, pp. 1 - 23. doi: 10.48550/arXiv.2503.13189.en_US
dc.identifier.urihttps://bura.brunel.ac.uk/handle/2438/31972-
dc.descriptionData Availability: Components of the PPCG data set can be accessed through different portals in accordance with the required level of data protection for each data type. The main data constituents, and respective modes of access, are listed in detail in the companion manuscript by GM Jakobsdottir [ref. 19].en_US
dc.descriptionA preprint version of the article is available at arXiv:2503.13189v1 [q-bio.GN], https://arxiv.org/abs/2503.13189 . It has not been certified by peer review. Submission history: From: Emre Esenturk [v1] Mon, 17 Mar 2025 14:00:02 UTC (818 KB).-
dc.descriptionCode Availability: Codes are available to reviewers. Open-source repository will be made available at the time of publication.-
dc.description.abstractCancer progression involves the sequential accumulation of genetic alterations that cumulatively shape the tumour phenotype. In prostate cancer, tumours can follow divergent evolutionary trajectories that lead to distinct subtypes, but the causes of this divergence remain unclear. While causal inference could elucidate the factors involved, conventional methods are unsuitable due to the possibility of unobserved confounders and ambiguity in the direction of causality. Here, we propose a method that circumvents these issues and apply it to genomic data from 829 prostate cancer patients. We identify several genetic alterations that drive divergence as well as others that prevent this transition, locking tumours into one trajectory. Further analysis reveals that these genetic alterations may cause each other, implying a positive-feedback loop that accelerates divergence. Our findings provide insights into how cancer subtypes emerge and offer a foundation for genomic surveillance strategies aimed at monitoring the progression of prostate cancer.en_US
dc.description.sponsorshipCentro Nacional de Investigaciones Oncológicas (CNIO), which is funded by the Instituto de Salud Carlos III and recognized by the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033) as a ‘Severo Ochoa’ Centre of Excellence (ref. CEX2019000891-S). Both A.F.-S. and G.M. also received support from Spanish Ministry of Science and Innovation grants PID2019-111356RA-I00 and PID2023-151298OB-I00 (MCIN/AEI/ 10.13039/501100011033). Additionally, A.F.-S. was awarded a fellowship from La Caixa Foundation (ID 100010434; LCF/BQ/DR21/11880009). V.J.G. acknowledges infrastructure backing from the NIHR Cambridge Biomedical Research Centre (BRC-1215–20014). V.M.H. received support from the Petre Foundation via the University of Sydney Foundation (Australia). H.H.H. is supported by project grants from the Canadian Institutes of Health Research (CIHR) (142246, 152863, 152864, 159567 and 438793). This work was also funded by NHMRC project grants 1104010 (C.M.H., N.M.C.) and 1047581 (C.M.H., N.M.C.), as well as through a federal grant from the Australian Department of Health and Ageing awarded to the Epworth Cancer Centre, Epworth Hospital (N.M.C., C.M.H.). We acknowledge further financial support from Australian Prostate Cancer Research and the University of Melbourne, Australia. M.L. received funding from National Cancer Institute grants P50CA211024, P01CA265768, R01 CA259200, from the U.S.A. Department of Defense (DoD) grants PC160357 and PC200390, as well as from the Prostate Cancer Foundation (22CHAL05). Additional support for SAPCS analytical costs came from the U.S. National Institute of Health (NIH) National Cancer Institute (NCI) Award R01CA285772-01 and a U.S. Prostate Cancer Foundation (PCF) Challenge Award (2023CHAL4150). Genomic sequencing and investigation of Southern African Prostate Cancer Study (SAPCS) data received funding from the U.S. Congressionally Directed Medical Research Programs (CDMRP) Prostate Cancer Research Program (PCRP), which included an Idea Development Award (PC200390, TARGET Africa) and HEROIC Consortium Awards (PC210168 and PC230673, HEROIC PCaPH Africa1K). R.M. and A.T.P. are supported by The Lorenzo and Pamela Galli Medical Research Trust, and A.T.P. also holds an Investigator Grant (2026643) from the National Health and Medical Research Council (NHMRC). B.P. is the recipient of a Victorian Health and Medical Research Fellowship awarded by the Victoria State Government, Australia. K.D.S. is funded by The Novo Nordisk Foundation (grant nos. NNF20OC0059410, NNF21OC0071712), The Danish Cancer Society (grant no. R352-A20573), and Independent Research Fund Denmark (grant no. 9039-00084B). J.R. acknowledges support from a CIHR Project Grant (grant no. PJT-162410) and an Investigator Award from the Ontario Institute for Cancer Research (OICR), which is itself funded by the Government of Ontario. Work at the University of Konstanz was supported by the university and an Exploration Grant from the Boehringer Ingelheim Foundation to A.J.G. J.W. received grants from the Danish Cancer Society (#R147-A9843, #R374-A22518), the Danish Council for Independent Research (#8020-00282, #3101-00177A), the Novo Nordisk Foundation (#NNF200C0060141), and Sygeforsikringen Danmark (#2022-0198). A.L. is supported by Cancer Research UK (C57899/A25812), The John Fell Fund (0012782), the Health Technology Assessment (NIHR 131233), and the John Black Charitable Foundation (TRANSLATE Triallinked biobank). Y-J.L. receives funding from Orchid, Prostate Cancer Research UK & Movember (MA-CT20-011, RIA22-ST2-006) and Cancer Research UK (C16420/A18066). A full list of funding organizations for the Pan Prostate Cancer Group is provided in a companion manuscript [ref. 19: to be published as supplementary material in due course].en_US
dc.format.mediumElectronic-
dc.language.isoen_USen_US
dc.publisherCornell Universityen_US
dc.relation.urihttps://arxiv.org/abs/2503.13189-
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 4.0 International-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/-
dc.subjectcausalityen_US
dc.subjectcausal inferenceen_US
dc.subjectcancer evolutionen_US
dc.subjectevolutionary divergenceen_US
dc.subjectprostate 90 canceren_US
dc.subjectgenomics (q-bio.GN)-
dc.titleCauses of evolutionary divergence in prostate canceren_US
dc.typePreprinten_US
dc.identifier.doihttps://doi.org/10.48550/arXiv.2503.13189-
dc.identifier.eissn2331-8422-
dc.rights.licensehttps://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.en-
dc.rights.holderThe Author(s)-
Appears in Collections:Dept of Computer Science Research Papers

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