Divergent Clonal Evolution and Early Dissemination Promote Genetic Heterogeneity of Metastases in Castration-Resistant Prostate Cancer.

ABSTRACT: Lethal prostate cancer has passed through at least two evolutionary bottlenecks: acquisition of metastatic potential and development of castration resistance. A better understanding of how this affects genetic heterogeneity across metastatic sites is needed to develop strategies to block metastatic spread and to overcome resistance. By leveraging deep whole-exome sequencing of 93 tumors from 26 patients, we examined patterns of metastatic dissemination and clonal evolution of prostate cancer. Phylogenetic reconstruction and mathematical modeling enabled quantification of the number of mutations and clones in the cancer ecosystem and characterization of each patient's disease as an evolutionary process. Although mutations of the earliest pathogenic genetic drivers of prostate cancer were tr

SUBMITTER: Hosseini N 

PROVIDER: S-EPMC12580794 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature