ERG alterations and mTOR pathway activation in primary prostate carcinomas developing castration-resistance

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Bone metastasis is a common complication of prostate cancer.
• Reliable biomarkers for predicting bone metastasis risk and timing are currently lacking.

Purpose of the Study:

• To investigate molecular alterations in primary prostate cancers associated with bone metastasis.
• To assess the utility of next-generation sequencing and immunohistochemistry for characterizing prostate cancer molecular features.

Main Methods:

• Analyzed 12 primary prostate cancer samples using targeted next-generation DNA and RNA sequencing.
• Assessed mutations, copy number alterations, and gene fusions.
• Utilized immunohistochemistry to evaluate ETS gene rearrangements (TMPRSS2-ERG) and mTOR pathway activation.

Main Results:

• Detected ETS family gene rearrangements in 10 cancers, PTEN alterations in 6, and TP53 alterations in 5.
• Found TMPRSS2-ERG fusions in 9 samples, correlating with increased ERG expression.
• Observed mTOR pathway activation in 6 patients, with a trend towards prevalence in late-metastatic cases (p=0.08).

Conclusions:

• Simultaneous next-generation sequencing is feasible on formalin-fixed paraffin-embedded tissues for comprehensive molecular profiling.
• This approach, combined with ERG and mTOR pathway assessment, can enhance prostate cancer characterization.
• Potential impact on clinical decision-making for managing prostate cancer bone metastasis.