Aligning germline and somatic mutations in prostate cancer. Are genetics changing practice?

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Prostate cancer (PCa) exhibits molecular alterations primarily in androgen receptor (AR) pathway and DNA repair deficiency.
• Germline mutations in BRCA2 and HOXB13, and somatic alterations in AR and TP53 are significant in PCa.
• Current genetic testing for PCa is evolving, with available molecular tests guiding clinical practice.

Purpose of the Study:

• To review the current status of germline and somatic genetic testing for prostate cancer (PCa).
• To assess the relevance of genetic testing for PCa in clinical practice.
• To analyze current guidelines and feasibility of genetic testing in PCa management.

Main Methods:

• A narrative synthesis of molecular profiles and their clinical context.
• Analysis of current genetic testing guidelines and their clinical feasibility.
• Reporting of genetic sequencing results and functional genomic scores for PCa.

Main Results:

• Molecular alterations in PCa involve AR pathway disruption and DNA repair deficiency.
• BRCA2 and HOXB13 are key germline mutation genes; AR and TP53 are frequent somatic alterations in metastatic PCa.
• Approved genetic tests focus on BRCA1/2 and DNA mismatch repair deficiency, guiding targeted therapies like PARP inhibitors and PSMA-guided radiotherapy.

Conclusions:

• Consensus is needed to align germline and somatic molecular analysis in metastatic PCa.
• Continuous updating of guidelines is essential due to rapid advances in PCa genetics.
• Further studies are required to evaluate the benefits of genetic testing in PCa management.