Genomic evolution shapes prostate cancer disease type.
Woodcock DJ., Sahli A., Teslo R., Bhandari V., Gruber AJ., Ziubroniewicz A., Gundem G., Xu Y., Butler A., Anokian E., Pope BJ., Jung C-H., Tarabichi M., Dentro SC., Farmery JHR., CRUK ICGC Prostate Group None., Van Loo P., Warren AY., Gnanapragasam V., Hamdy FC., Bova GS., Foster CS., Neal DE., Lu Y-J., Kote-Jarai Z., Fraser M., Bristow RG., Boutros PC., Costello AJ., Corcoran NM., Hovens CM., Massie CE., Lynch AG., Brewer DS., Eeles RA., Cooper CS., Wedge DC.
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.