Genomic and Transcriptomic Profiling of Radiation-Resistant, Locally Recurrent Prostate Cancer.

Area of Science:

• Oncology
• Genomics
• Cancer Biology

Background:

• The biological underpinnings of locally radiorecurrent prostate cancer (LRR-PCa) remain largely unexplored.
• Understanding LRR-PCa is crucial for developing effective salvage therapies.

Purpose of the Study:

• To investigate the genomic and transcriptomic characteristics of LRR-PCa.
• To compare the molecular landscape of LRR-PCa with treatment-naïve prostate cancer.

Main Methods:

• Targeted DNA sequencing and RNA expression analysis were performed on 41 LRR-PCa tumors.
• Genomic alterations and transcriptomic data were compared to The Cancer Genome Atlas and Decipher Genomics Resource for Intelligent Discovery cohorts.

Main Results:

• LRR-PCa tumors frequently showed pathologic upgrading and increased single-nucleotide variations (SNVs) in genes linked to aggressiveness and DNA repair (e.g., FAT1, RAD51B, BRCA2).
• The LRR-PCa cohort displayed higher Decipher scores, a more basal subtype, and reduced androgen receptor activity compared to controls.
• Significant differences were observed in mutation frequencies and gene expression profiles (P < .001).

Conclusions:

• LRR-PCa possesses a unique genomic and transcriptomic signature distinct from de novo prostate cancer.
• Enrichment of SNVs in aggressive/DNA repair genes, higher Decipher scores, basal subtype, and altered androgen receptor activity characterize LRR-PCa.