Integrative genomic profiling of human prostate cancer

Area of Science:

• Genomics
• Oncology
• Molecular Biology

Background:

• Prostate cancer genome annotation is crucial for understanding and treating the disease.
• Previous studies have focused on specific genetic alterations, but a comprehensive analysis integrating multiple genomic data types is needed.

Purpose of the Study:

• To comprehensively annotate the genomes of prostate cancer tumors.
• To identify novel oncogenes and tumor suppressors in prostate cancer.
• To explore the relationship between genomic alterations and clinical outcomes.

Main Methods:

• Concordant assessment of DNA copy number, mRNA expression, and exon resequencing in 218 prostate cancer tumors.
• Analysis of DNA copy-number data to identify genomic alterations.
• Correlation of genomic findings with clinical outcome data.

Main Results:

• The nuclear receptor coactivator NCOA2 was identified as an oncogene in approximately 11% of prostate tumors.
• The TMPRSS2-ERG fusion was associated with a novel deletion at chromosome 3p14, implicating FOXP1, RYBP, and SHQ1 as potential tumor suppressors.
• DNA copy-number alterations robustly defined low- and high-risk disease clusters, outperforming Gleason score for risk stratification.

Conclusions:

• NCOA2 is a potential therapeutic target in a subset of prostate cancers.
• FOXP1, RYBP, and SHQ1 may function as cooperative tumor suppressors in prostate cancer.
• Genomic copy-number alterations provide a powerful tool for refining prostate cancer risk assessment beyond traditional methods.