Profiling of pharmacogenomic variants in CYP2D6 and DPYD in indigenous Arab breast cancer patients

Aim: The indigenous Arab population is underrepresented in genomic studies and the landscape of actionable pharmacogenomic variants among Arab breast cancer patients remains unclear. Materials & methods: Exome sequencing was performed on 220 unselected Arab female breast cancer patients and germline variants in CYP2D6 and DPYD were profiled using a deep learning method. Results: In total, 13 (5.9%) patients had clinically actionable results and 56 (25.5%) carried an allele in DYPD or CYP2D6 with unknown impact on drug metabolism. In addition, four unique novel missense variants were discovered, including one in CYP2D6 (p.Arg64Leu) with high predicted pathogenicity. Conclusion: A nontrivial subset of Arab breast cancer patients can potentially benefit from pretreatment molecular profiling, and further study is needed to improve characterization of the pharmacogenomic landscape.

Automated summary

The aim of this study was to investigate the actionable pharmacogenomic variants among Arab breast cancer patients. Exome sequencing was performed on 220 patients, and it was found that a nontrivial subset of patients had clinically actionable results and carried variants with unknown impact on drug metabolism. Additionally, novel missense variants were discovered, indicating the need for further study on the pharmacogenomic landscape.