Molecular stratification of SPOP-mutant prostate cancer demonstrates Wnt signaling and replication stress signatures in diverse patient populations.

SPOP-mutant prostate cancer exhibits conserved Wnt pathway dysregulation and diverse transcriptional signatures across racial groups, highlighting its molecular distinctiveness.

• Why it matters: Understanding the genomic and transcriptional features of SPOP-mutant prostate cancer across diverse populations is crucial for developing targeted therapies and addressing health disparities.
• What they did: The study analyzed genomic profiles from 273 patients, including 40 with SPOP mutations, and performed RNA sequencing on 102 cases to identify alterations related to disease stage and race.
• The result: Findings reveal a consistent Wnt pathway activation and race-specific transcriptional programs, suggesting that SPOP-mutant tumors have distinct, potentially targetable vulnerabilities influenced by patient ancestry.