Genomic evolution shapes prostate cancer disease type

Journal article

H.R.F. was supported by a Cancer Research UK Programme Grant to Simon Tavaré (C14303/A17197), as, partially, was A.G.L. A.G.L. acknowledges the support of the University of St Andrews. A.G.L. and J.H.R.F. also acknowledge the support of the Cambridge Cancer Research Fund.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.Peer reviewe

Authors: Woodcock, DJ; Sahli, A; Teslo, R; Bhandari, V; Gruber, AJ

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell Genomics
• Volume: 4
• Issue: 3
• Pages: 100511-100511
• Article number: 100511
• Publication date: 2024-02-29
• DOI: 10.1016/j.xgen.2024.100511
• EISSN: 2666-979X
• ISSN: 2666-979X
• Language: English
• Keywords: Evolutionary biology; Prostate cancer; Cancer; Genetics; Androgen receptor; Computational biology; Biology; Medicine; Internal medicine; Disease; Prostate; Chromoplexy; PCA3; Somatic evolution in cancer; Cancer research