Whole genome sequencing of 378 prostate cancer metastases reveals tissue selectivity for mismatch deficiency with potential therapeutic implications.

ABSTRACT:

Background

Survival of patients with metastatic castration-resistant prostate cancer (mCRPC) depends on the site of metastatic dissemination.

Methods

Patients with mCRPC were prospectively included in the CPCT-02 metastatic site biopsy study. We evaluated whole genome sequencing (WGS) of 378 mCRPC metastases to understand the genetic traits that affect metastatic site distribution.

Results

Our findings revealed that RB1, PIK3CA, JAK1, RNF43, and TP53 mutations are the most frequent genetic determinants associated with site selectivity for metastatic outgrowth. Furthermore, we explored mutations in the non-coding genome and found that androgen receptor (AR) chromatin binding sites implicated in metastatic prostate cancer differ in mutation frequencies between metastati

SUBMITTER: Vis DJ 

PROVIDER: S-EPMC11927350 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature