Genomic evolution shapes prostate cancer disease type

• Published in: Cell genomics 2024-03, Vol.4 (3), p.100511-100511, Article 100511
• Main Authors: Woodcock, Dan J., Sahli, Atef, Teslo, Ruxandra, Bhandari, Vinayak, Gruber, Andreas J., Ziubroniewicz, Aleksandra, Gundem, Gunes, Xu, Yaobo, Butler, Adam, Anokian, Ezequiel, Pope, Bernard J., Jung, Chol-Hee, Tarabichi, Maxime, Dentro, Stefan C., Farmery, J. Henry R., Van Loo, Peter, Warren, Anne Y., Gnanapragasam, Vincent, Hamdy, Freddie C., Bova, G. Steven, Foster, Christopher S., Neal, David E., Lu, Yong-Jie, Kote-Jarai, Zsofia, Fraser, Michael, Bristow, Robert G., Boutros, Paul C., Costello, Anthony J., Corcoran, Niall M., Hovens, Christopher M., Massie, Charlie E., Lynch, Andy G., Brewer, Daniel S., Eeles, Rosalind A., Cooper, Colin S., Wedge, David C.
• Format: Article
• Language: English
• Subjects: AR binding; cancer evolution; evotype model; evotypes; ordering; prostate cancer
• ISSN: 2666-979X; 2666-979X
• DOI: 10.1016/j.xgen.2024.100511

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 Alternative 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. [Display omitted] •Analysis of genomic data from localized prostate cancer reveals divergent evolution•The shift away from the canonical trajectory is characterized by AR dysregulation•Tumors can be classified into evotypes according to evolutionary trajectory•The evotype model unifies many previous molecular observations Woodcock et al. show that individual evolutionary trajectories in prostate cancer can be classified into two broad categories, termed evotypes. This motivates a model of prostate cancer evolution in which Alternative-evotype tumors diverge from those of the Canonical-evotype due to acquired genetic alterations that alter the androgen receptor cistrome.