Two types of Prostate Cancer – one is far more lethal
Genomic evolution shapes prostate cancer disease type
Cell Geonomics VOL 4, # 3, 100511, MARCH 13, 2024 https://doi.org/10.1016/j.xgen.2024.100511
Dan J. Woodcock, Atef Sahli, Ruxandra Teslo, Rosalind A. Eeles 43, Colin S. Cooper 43, David C. Wedge 43, 46
Highlights
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
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.
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