805 Comprehensive Genomic Analysis of Advanced Prostate Cancer from a Large Institutional Cohort
Recommended Citation
Ozcan GG, Ozcan K, Alhamar M, Dadhania V, Gupta N, Hassan O. 805 Comprehensive Genomic Analysis of Advanced Prostate Cancer from a Large Institutional Cohort. Lab Invest 2026; 106(3).
Document Type
Conference Proceeding
Publication Date
3-23-2026
Publication Title
Lab Invest
Keywords
circulating tumor DNA, transcriptome, adult, aged, chromatin remodeling, conference abstract, controlled study, DNA repair, female, follow up, gene fusion, genomic instability, high throughput sequencing, human, human tissue, major clinical study, male, metastasis, mutation rate, personalized cancer therapy, primary tumor, prostate cancer, prostate carcinoma, RNA sequencing, signal transduction, special situation for pharmacovigilance, tumor growth
Abstract
Disclosures: Gamze Gokturk Ozcan: None; Kerem Ozcan: None; Mohamed Alhamar: None; Vipulkumar Dadhania: None; Nilesh Gupta: None; Oudai Hassan: None Background: Advanced-stage prostate carcinoma (PCa) is characterized by a heterogeneous spectrum of genomic alterations that drive tumor progression, treatment resistance, and metastasis. Comprehensive genomic profiling (CGP) enables a deeper understanding of these molecular events and informs precision oncology strategies for patients with advanced disease. Design: Patients with advanced-stage PCa who underwent genomic profiling at our institution between 2017-2025 were included in this study. Targeted next-generation sequencing (NGS) of up to 648 cancer-associated genes was performed on tumor tissue samples (n=469). Whole-transcriptome RNA sequencing was utilized to identify gene fusions (n=179) and circulating tumor DNA (ctDNA) analysis was conducted using peripheral blood specimens (n=441). Mutation frequencies were calculated as the proportion of cases harboring a specific alteration among all samples with at least one detectable genomic event. Results: The study included 573 patients with advanced-stage prostate carcinoma (median age 70 years, range 40-95), encompassing a total of 1,089 analyzed samples (1-5 per patient): primary tumors (n=490), metastatic lesions (n=158), and peripheral blood specimens (n=441). The majority of patients had Grade Group (GG) 5 tumors, followed by GG3 and GG4 (39%, 18%, and 16%, respectively). 11% of cases (n=61) were diagnosed based on metastatic biopsies. At last follow-up, 415 patients were alive, 137 had died, 21 were lost to follow-up. The most frequently altered genes across all samples were TP53 (40%), TMPRSS2::ERG (19%), ATM (15%), PTEN (14%), FOXA1 (10%), APC (10%), BRCA2 (10%), NF1 (9%), AR (8%), and SPOP (8%) (Figure 1). Pathway-level analysis revealed recurrent alterations involving the cell-cycle/TP53 (34%), DNA-repair (25%), and PI3K-AKT-mTOR (23%). and chromatin-remodeling (22%) pathways, with additional presence of AR-signaling (17%) and RTK/growth-factor alteration (18%) events. MSI-high status was detected in 1.1% (n=13) of samples. Collectively, these findings highlight the predominance of genomic instability and DNA-repair defects in advanced-stage prostate carcinoma. [Formula presented] Conclusions: Advanced-stage PCa exhibits a heterogeneous genomic landscape characterized by frequent TP53, DNA-repair, and PI3K-pathway alterations, together with recurrent AR-signaling and RTK alteration events. Detection of recurrent and potentially targetable alterations highlights the clinical utility of CGP in informing precision management of advanced prostate cancer.
Volume
106
Issue
3
