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

SPOP-mutant prostate cancer exhibits Wnt pathway dysregulation and diverse transcriptional signatures across racial groups, with 40 tumors analyzed for genomic and transcriptomic features.

• Why it matters: Understanding the molecular features of SPOP-mutant prostate cancer across different populations is crucial for identifying targeted therapies and addressing health disparities.
• What they did: The study integrated genomic profiles from 273 patients, including 40 with SPOP mutations, and performed RNA sequencing on 102 cases to analyze alterations across disease stages and races.
• The result: SPOP-mutant tumors showed APC co-alterations supporting Wnt pathway dysregulation; race-stratified analysis revealed conserved structural repression but divergent activation of inflammatory and metabolic programs, indicating potential heterogeneous therapeutic vulnerabilities.