Pharmacogenomic Testing Evolves From Targeted Genotyping Toward Sequencing-Based Approaches
This comprehensive review traces the 60-year evolution of pharmacogenomic testing from single-gene assays to multiplexed panels, and previews the anticipated transition to NGS-based methods. Key technical challenges persist for complex loci such as CYP2D6, HLA-A, and HLA-B, which require specialized approaches due to high polymorphism and copy-number variation. The authors discuss standardization efforts, harmonization with broader genomic medicine, and emerging frontiers including pharmacoepigenetics, polygenic risk scoring, and large-scale functional genomics for rare variant classification.
The original study
Pharmacogenomic Testing in the Clinical Laboratory: Historical Progress and Future Opportunities.
- Authors
- Moyer AM, Black JL
- Journal
- Annals of laboratory medicine
- Type
- Journal Article, Review
- PMID
- 40170583
Original abstract
Pharmacogenomics is a rapidly evolving field with a strong foundation in basic science dating back to 1960. Pharmacogenomic findings have been translated into clinical care through collaborative efforts of clinical practitioners, pharmacists, clinical laboratories, and research groups. The methods used have transitioned from targeted genotyping of relatively few variants in individual genes to multiplexed multi-gene panels, and sequencingbased methods are likely on the horizon; however, no system exists for classifying and reporting rare variants identified via sequencing-based approaches. Laboratory testing in pharmacogenomics is complex for several genes, including cytochrome P450 2D6 (CYP2D6), HLA-A, and HLA-B , owing to a high degree of polymorphisms, homology with other genes, and copy-number variation. These loci require specialized methods and familiarity with each gene, which may persist during the transition to next-generation sequencing. Increasing implementation across laboratories and clinical facilities has required cooperative efforts to develop standard testing targets, nomenclature, and reporting practices and guidelines for applying the results clinically. Beyond standardization, harmonization between pharmacogenomics and the broader field of genomic medicine may be essential for facilitating further adoption and realizing the full potential of personalized medicine. In this review, we describe the evolution of clinical laboratory testing for pharmacogenomics, including standardization efforts and the anticipated transition from targeted genotyping to sequencing-based pharmacogenomics. We speculate on potential upcoming developments, including pharmacoepigenetics, improved understanding of the impact of non-coding variants, use of large-scale functional genomics to characterize rare variants, and a renewed interest in polygenic risk or combinatorial approaches, which will drive the progression of the field.