Genomic evolution shapes prostate cancer disease type

CRUK-ICGC Prostate Group, Dan J Woodcock, Atef Sahli, Ruxandra Teslo, Vinayak Bhandari, Andreas J Gruber, Aleksandra Ziubroniewicz, Gunes Gundem, Yaobo Xu, Adam Butler, Ezequiel Anokian, Bernard J Pope, Chol-Hee Jung, Maxime Tarabichi, Stefan C Dentro, J Henry R Farmery, Peter Van Loo, Anne Y Warren, Vincent Gnanapragasam, Freddie C HamdyG Steven Bova, Christopher S Foster, David E Neal, Yong-Jie Lu, Zsofia Kote-Jarai, Robert G Bristow, Paul C Boutros, Anthony J Costello, Niall M Corcoran, Christopher M Hovens, Charlie E Massie, Andy G Lynch, Daniel S Brewer*, Rosalind A Eeles*, Colin S Cooper*, David C Wedge*

*Corresponding author for this work

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Abstract

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Aalternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.

Original languageEnglish
Article number100511
Number of pages31
JournalCell Genomics
Volume4
Issue number13
Early online date13 Mar 2024
DOIs
Publication statusE-pub ahead of print - 13 Mar 2024

Keywords

  • Prostate cancer
  • Cancer evolution
  • Evotype model
  • Evotypes
  • AR binding
  • Ordering

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