Landscape of Allele-Specific Expression in Prostate Cancer Reveals Recurrent, Stage-Specific Events in AR Signaling...

Area of Science:

• Genomics
• Cancer Biology
• Bioinformatics

Background:

• Cis-regulatory alterations in prostate cancer (PCa) are not well understood, limiting the discovery of driver genes and therapeutic targets.
• Allele-specific expression (ASE) analysis offers a powerful approach to uncover these regulatory events.

Purpose of the Study:

• To comprehensively study cis-regulatory alterations in PCa by identifying genes with allele-specific expression (ASE).
• To develop a computational framework (CASEDI) for prioritizing cancer drivers by integrating ASE and clinical data.
• To identify novel therapeutic targets for localized PCa and metastatic castration-resistant PCa (mCRPC).

Main Methods:

• Identification of genes with allele-specific expression (ASE) in localized PCa and mCRPC samples.
• Development of CASEDI, a computational framework integrating ASE and clinical data for cancer driver prioritization.
• Analysis of recurrent ASE events and tumor-enriched ASE in prostate tissues.

Main Results:

• CASEDI identified recurrently expressed genes and altered expression in PCa, including ACSM1.
• Metastatic castration-resistant PCa (mCRPC) samples showed enriched ASE in DNA repair and resistance pathways.
• A gene signature based on monoallelic expression (MAE) in mCRPC identified localized patients with poorer prognosis.

Conclusions:

• The study developed a novel framework (CASEDI) for identifying PCa drivers using ASE data.
• A comprehensive dataset of ASE in PCa was generated, highlighting candidate targets for tumorigenesis and metastasis.
• ASE analysis expands the understanding of cis-regulatory events in PCa, informing the discovery of new therapeutic targets.