Genomic alterations in neuroendocrine prostate cancer: A systematic review and meta-analysis
Junru Chen1,2,3,4, Mingchen Shi2,3,4, Stephen Yiu Chuen Choi2,3,4
1Department of Urology, Institute of Urology, West China Hospital Sichuan University Chengdu Sichuan China.
Background:
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. We performed a systematic review and meta-analysis to evaluate the prevalence of genomic alterations in NEPC and better understand its molecular features to potentially inform precision medicine.
Methods:
EMBASE, PubMed, and Cochrane Central Register of Controlled Trials databases were searched for eligible studies until March 2022. Study qualities were assessed using the Q-genie tool. The prevalence of gene mutations and copy number alterations (CNAs) were extracted, and meta-analysis was performed using R Studio with meta package.
Results:
A total of 14 studies with 449 NEPC patients were included in this meta-analysis. The most frequently mutated gene in NEPC was TP53 (49.8%), and the prevalence of deleterious mutations in ATM/BRCA was 16.8%. Common CNAs in NEPC included RB1 loss (58.3%), TP53 loss (42.8%), PTEN loss (37.0%), AURKA amplification (28.2%), and MYCN amplification (22.9%). RB1/TP53 alterations and concurrent RB1 and TP53 alterations were remarkably common in NEPC, with a prevalence of 83.8% and 43.9%, respectively. Comparative analyses indicated that the prevalence of (concurrent) RB1/TP53 alterations was significantly higher in de novo NEPC than in treatment-emergent NEPC (t-NEPC).
Conclusions:
This study presents the comprehensive prevalence of common genomic alterations and potentially actionable targets in NEPC and reveals the genomic differences between de novo NEPC and t-NEPC. Our findings highlight the importance of genomic testing in patients for precision medicine and provide insights into future studies exploring different NEPC subtypes.
Insights
Genomic alterations like TP53 mutations and RB1 loss are common in neuroendocrine prostate cancer (NEPC). These findings are crucial for understanding NEPC subtypes and guiding precision medicine approaches.
Area of Science:
- Oncology
- Genetics
- Genomics
Background:
- Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer.
- Understanding NEPC's molecular landscape is vital for developing targeted therapies.
- Genomic alterations play a significant role in NEPC development and progression.
Purpose of the Study:
- To systematically review and analyze the prevalence of genomic alterations in NEPC.
- To identify common gene mutations and copy number alterations (CNAs) in NEPC patients.
- To inform precision medicine strategies by elucidating NEPC's molecular features.
Main Methods:
- Systematic review and meta-analysis of studies published until March 2022.
- Searched EMBASE, PubMed, and Cochrane Central Register of Controlled Trials databases.
- Assessed study quality using the Q-genie tool and performed meta-analysis using R Studio.
Main Results:
- Analysis included 14 studies with 449 NEPC patients.
- Frequent mutations: TP53 (49.8%), ATM/BRCA (16.8%).
- Common CNAs: RB1 loss (58.3%), TP53 loss (42.8%), PTEN loss (37.0%), AURKA amplification (28.2%), MYCN amplification (22.9%).
- RB1/TP53 alterations (83.8%) and concurrent RB1/TP53 alterations (43.9%) were highly prevalent.
- RB1/TP53 alterations were more common in de novo NEPC than treatment-emergent NEPC (t-NEPC).
Conclusions:
- This meta-analysis provides a comprehensive overview of genomic alterations in NEPC.
- Identified key alterations and potential therapeutic targets for NEPC.
- Genomic testing is essential for personalized treatment of NEPC patients.
- Findings reveal distinct genomic profiles between de novo and t-NEPC, guiding future research.
