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Homologous recombination repair gene mutations in Malaysian prostate cancer patients

Hamidreza Saeidi1, Chandramathi Samudi Raju2, Patimah Ismail3

  • 1Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia. hamidrezasaeidi@protonmail.com.

Cellular and Molecular Biology (Noisy-Le-Grand, France)
|February 21, 2023
PubMed

Insights

Identifying genetic alterations in homologous recombination repair (HRR) genes is crucial for prostate cancer treatment. This study found actionable mutations in HRR genes, suggesting potential benefits from targeted therapies like PARP inhibitors.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Genetic alterations in homologous recombination repair (HRR) genes increase prostate cancer risk.
  • Patients with HRR mutations may respond to targeted therapies.

Purpose of the Study:

  • To identify genetic alterations in HRR genes for potential targeted prostate cancer treatment.
  • To investigate mutations in 27 HRR genes and 5 cancer-associated genes.

Main Methods:

  • Targeted next-generation sequencing (NGS) was employed.
  • Analysis included protein-coding regions of 27 HRR genes and hotspots of 5 cancer-associated genes.
  • Samples analyzed: four FFPE and three blood samples from prostate cancer patients.

Main Results:

  • Identified mutations in TP53 and KRAS.
  • Detected variants of uncertain significance and conflicting interpretations in BRCA2, STK11, and RAD51B.
  • Discovered novel variants in CDK12 and ATM, and a drug response variant in TP53.
  • Found actionable pathogenic and potentially pathogenic variants linked to PARP inhibitor response.

Conclusions:

  • Actionable genetic alterations in HRR genes were identified in prostate cancer patients.
  • These findings suggest potential efficacy of targeted therapies, including PARP inhibitors.
  • Further research in larger cohorts is necessary to confirm the association between HRR mutations and prostate cancer outcomes.

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