Causes of evolutionary divergence in prostate cancer

Emre Esentürk; Atef Sahli; Valeriia Haberland; Aleksandra Ziuboniewicz; Christopher Wirth; G Steven Bova; Robert G Bristow; Mark N Brook; Benedikt Brors; Adam Butler; Géraldine Cancel-Tassin; Kevin Cl Cheng; Colin S Cooper; Niall M Corcoran; Olivier Cussenot; Ros A Eeles; Francesco Favero; Clarissa Gerhauser; Abraham Gihawi; Etsehiwot G Girma; Vincent J Gnanapragasam; Andreas J Gruber; Anis Hamid; Vanessa M Hayes; Housheng Hansen He; Christopher M Hovens; Eddie Luidy Imada; G Maria Jakobsdottir; Chol-Hee Jung; Francesca Khani; Zsofia Kote-Jarai; Philippe Lamy; Gregory Leeman; Massimo Loda; Pavlo Lutsik; Luigi Marchionni; Ramyar Molania; Anthony T Papenfuss; Diogo Pellegrina; Bernard Pope; Lucio R Queiroz; Tobias Rausch; Jüri Reimand; Brian Robinson; Thorsten Schlomm; Karina D Sørensen; Sebastian Uhrig; Joachim Weischenfeldt; Yaobo Xu; Takafumi N Yamaguchi; Claudio Zanettini; Andy G Lynch; David C Wedge; Daniel S Brewer; Dan J Woodcock

Causes of evolutionary divergence in prostate cancer

Emre Esentürk^*, Atef Sahli, Valeriia Haberland, Aleksandra Ziuboniewicz, Christopher Wirth, G Steven Bova, Robert G Bristow, Mark N Brook, Benedikt Brors, Adam Butler, Géraldine Cancel-Tassin, Kevin Cl Cheng, Colin S Cooper, Niall M Corcoran, Olivier Cussenot, Ros A Eeles, Francesco Favero, Clarissa Gerhauser, Abraham Gihawi, Etsehiwot G GirmaVincent J Gnanapragasam, Andreas J Gruber, Anis Hamid, Vanessa M Hayes, Housheng Hansen He, Christopher M Hovens, Eddie Luidy Imada, G Maria Jakobsdottir, Chol-Hee Jung, Francesca Khani, Zsofia Kote-Jarai, Philippe Lamy, Gregory Leeman, Massimo Loda, Pavlo Lutsik, Luigi Marchionni, Ramyar Molania, Anthony T Papenfuss, Diogo Pellegrina, Bernard Pope, Lucio R Queiroz, Tobias Rausch, Jüri Reimand, Brian Robinson, Thorsten Schlomm, Karina D Sørensen, Sebastian Uhrig, Joachim Weischenfeldt, Yaobo Xu, Takafumi N Yamaguchi, Claudio Zanettini, Andy G Lynch, David C Wedge, Daniel S Brewer, Dan J Woodcock^*

^*Corresponding author af dette arbejde

Finsenlaboratoriet

Abstract

Cancer 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.

Originalsprog	Engelsk
Status	Udgivet - 17 mar. 2025

Navn	ArXiv
ISSN	2331-8422

Citationsformater

Esentürk, E, Sahli, A, Haberland, V, Ziuboniewicz, A, Wirth, C, Bova, GS, Bristow, RG, Brook, MN, Brors, B, Butler, A, Cancel-Tassin, G, Cheng, KC, Cooper, CS, Corcoran, NM, Cussenot, O, Eeles, RA, Favero, F, Gerhauser, C, Gihawi, A, Girma, EG, Gnanapragasam, VJ, Gruber, AJ, Hamid, A, Hayes, VM, He, HH, Hovens, CM, Imada, EL, Jakobsdottir, GM, Jung, C-H, Khani, F, Kote-Jarai, Z, Lamy, P, Leeman, G, Loda, M, Lutsik, P, Marchionni, L, Molania, R, Papenfuss, AT, Pellegrina, D, Pope, B, Queiroz, LR, Rausch, T, Reimand, J, Robinson, B, Schlomm, T, Sørensen, KD, Uhrig, S, Weischenfeldt, J, Xu, Y, Yamaguchi, TN, Zanettini, C, Lynch, AG, Wedge, DC, Brewer, DS & Woodcock, DJ 2025 'Causes of evolutionary divergence in prostate cancer' ArXiv.

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title = "Causes of evolutionary divergence in prostate cancer",

abstract = "Cancer 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.",

author = "Emre Esent{\"u}rk and Atef Sahli and Valeriia Haberland and Aleksandra Ziuboniewicz and Christopher Wirth and Bova, \{G Steven\} and Bristow, \{Robert G\} and Brook, \{Mark N\} and Benedikt Brors and Adam Butler and G{\'e}raldine Cancel-Tassin and Cheng, \{Kevin Cl\} and Cooper, \{Colin S\} and Corcoran, \{Niall M\} and Olivier Cussenot and Eeles, \{Ros A\} and Francesco Favero and Clarissa Gerhauser and Abraham Gihawi and Girma, \{Etsehiwot G\} and Gnanapragasam, \{Vincent J\} and Gruber, \{Andreas J\} and Anis Hamid and Hayes, \{Vanessa M\} and He, \{Housheng Hansen\} and Hovens, \{Christopher M\} and Imada, \{Eddie Luidy\} and Jakobsdottir, \{G Maria\} and Chol-Hee Jung and Francesca Khani and Zsofia Kote-Jarai and Philippe Lamy and Gregory Leeman and Massimo Loda and Pavlo Lutsik and Luigi Marchionni and Ramyar Molania and Papenfuss, \{Anthony T\} and Diogo Pellegrina and Bernard Pope and Queiroz, \{Lucio R\} and Tobias Rausch and J{\"u}ri Reimand and Brian Robinson and Thorsten Schlomm and S{\o}rensen, \{Karina D\} and Sebastian Uhrig and Joachim Weischenfeldt and Yaobo Xu and Yamaguchi, \{Takafumi N\} and Claudio Zanettini and Lynch, \{Andy G\} and Wedge, \{David C\} and Brewer, \{Daniel S\} and Woodcock, \{Dan J\}",

year = "2025",

month = mar,

day = "17",

language = "English",

series = "ArXiv",

type = "WorkingPaper",

}

TY - UNPB

T1 - Causes of evolutionary divergence in prostate cancer

AU - Esentürk, Emre

AU - Sahli, Atef

AU - Haberland, Valeriia

AU - Ziuboniewicz, Aleksandra

AU - Wirth, Christopher

AU - Bova, G Steven

AU - Bristow, Robert G

AU - Brook, Mark N

AU - Brors, Benedikt

AU - Butler, Adam

AU - Cancel-Tassin, Géraldine

AU - Cheng, Kevin Cl

AU - Cooper, Colin S

AU - Corcoran, Niall M

AU - Cussenot, Olivier

AU - Eeles, Ros A

AU - Favero, Francesco

AU - Gerhauser, Clarissa

AU - Gihawi, Abraham

AU - Girma, Etsehiwot G

AU - Gnanapragasam, Vincent J

AU - Gruber, Andreas J

AU - Hamid, Anis

AU - Hayes, Vanessa M

AU - He, Housheng Hansen

AU - Hovens, Christopher M

AU - Imada, Eddie Luidy

AU - Jakobsdottir, G Maria

AU - Jung, Chol-Hee

AU - Khani, Francesca

AU - Kote-Jarai, Zsofia

AU - Lamy, Philippe

AU - Leeman, Gregory

AU - Loda, Massimo

AU - Lutsik, Pavlo

AU - Marchionni, Luigi

AU - Molania, Ramyar

AU - Papenfuss, Anthony T

AU - Pellegrina, Diogo

AU - Pope, Bernard

AU - Queiroz, Lucio R

AU - Rausch, Tobias

AU - Reimand, Jüri

AU - Robinson, Brian

AU - Schlomm, Thorsten

AU - Sørensen, Karina D

AU - Uhrig, Sebastian

AU - Weischenfeldt, Joachim

AU - Xu, Yaobo

AU - Yamaguchi, Takafumi N

AU - Zanettini, Claudio

AU - Lynch, Andy G

AU - Wedge, David C

AU - Brewer, Daniel S

AU - Woodcock, Dan J

PY - 2025/3/17

Y1 - 2025/3/17

N2 - Cancer 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.

AB - Cancer 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.

M3 - Preprint

C2 - 40166741

T3 - ArXiv

BT - Causes of evolutionary divergence in prostate cancer

ER -

Causes of evolutionary divergence in prostate cancer

Abstract

Fingeraftryk

Citationsformater