Pharmacogenomic Testing in the Clinical Laboratory : Historical Progress and Future Opportunities

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 sequencing-based 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.