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.
Keywords
Cite
@article{arxiv.2503.13189,
title = {Causes of evolutionary divergence in prostate cancer},
author = {Emre Esenturk and Atef Sahli and Valeriia Haberland and Aleksandra Ziuboniewicz and Christopher Wirth and G. Steven Bova and Robert G Bristow and Mark N Brook and Benedikt Brors and Adam Butler and Géraldine Cancel-Tassin and Kevin CL Cheng and Colin S Cooper and Niall M Corcoran and Olivier Cussenot and Ros A Eeles and Francesco Favero and Clarissa Gerhauser and Abraham Gihawi and Etsehiwot G Girma and Vincent J Gnanapragasam and Andreas J Gruber and Anis Hamid and Vanessa M Hayes and Housheng Hansen He and Christopher M Hovens and Eddie Luidy Imada and G. Maria Jakobsdottir 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 Anthony T Papenfuss and Diogo Pellegrina and Bernard Pope and Lucio R Queiroz and Tobias Rausch and Jüri Reimand and Brian Robinson and Thorsten Schlomm and Karina D Sørensen and Sebastian Uhrig and Joachim Weischenfeldt and Yaobo Xu and Takafumi N Yamaguchi and Claudio Zanettini and Andy G Lynch and David C Wedge and Daniel S Brewer and Dan J Woodcock},
journal= {arXiv preprint arXiv:2503.13189},
year = {2025}
}