The Association for Molecular Pathology (AMP), a global molecular diagnostic professional society, published consensus recommendations to aid in the design and validation of clinical TPMT and NUDT15 genotyping assays, promote standardization of testing across different laboratories, and improve patient care.

The manuscript, “TPMT and NUDT15 Genotyping Recommendations: A Joint Consensus Recommendation of the Association for Molecular Pathology, Clinical Pharmacogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, European Society for Pharmacogenomics and Personalized Therapy, and Pharmacogenomics Knowledgebase,” was released online ahead of publication in The Journal of Molecular Diagnostics.

The AMP Pharmacogenetics (PGx) Working Group is developing a series of guidelines designed to help standardize clinical testing for frequently used genotyping assays. The latest TPMT and NUDT15 report builds on the earlier recommendations for clinical genotyping of CYP2C19CYP2C9, CYP2D6, and genes important for warfarin testing. The recommendations should be implemented together with other relevant clinical guidelines such as those issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC), Dutch Pharmacogenetics Working Group (DPWG), Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network of Pharmacogenetics, all of which focus primarily on the interpretation of PGx test results and therapeutic recommendations for specific drug–gene pairs.

“Clinical tests for genetic variants in TPMT and NUDT15 can identify individuals who are at increased risk of adverse drug toxicity with standard doses of thiopurine medications,” says Victoria M. Pratt, PhD, Co-Chair of the AMP PGx Working Group, Vice President of Molecular Diagnostics Quality Assessments at Optum Genomics, and Adjunct Professor of Medical and Molecular Genetics at Indiana University School of Medicine. “The AMP PGx Working Group was established to help standardize clinical testing across laboratories. This series of reports for TPMT, NUDT15, and many other frequently used PGx genotyping assays are designed to ensure the assays investigate the most clinically relevant variant alleles and enable healthcare professionals to provide high-quality patient care.”

Similar to the previous reports in the series, the new TPMT and NUDT15 report offers a two-tier categorization of alleles that are recommended for inclusion in clinical PGx genotyping assays. Using criteria such as allele frequencies in people of different genetic ancestries, the availability of reference materials, and other technical considerations, the AMP PGx Working Group recommended a minimum set of alleles and their defining variants that should be included in all clinical TPMT and NUDT15 genotyping tests (Tier 1). The team also defined a Tier 2 list of optional alleles that do not currently meet one or more of the criteria for inclusion in Tier 1.

These recommendations are meant to be a reference guide and not to be interpreted as a restrictive list. AMP intends to update these recommendations as new data and/or reference materials become available.

“PGx testing has become an important tool to help clinicians select medications and prescribe an appropriate dose for certain patients,” says Karen E. Weck, MD, Co-Chair of the AMP PGx Working Group and Director of Molecular Genetics and Pharmacogenomics and Professor of Pathology & Laboratory Medicine and Genetics at the University of North Carolina at Chapel Hill. “AMP is committed to collaborating with the broader laboratory community to continuously improve professional PGx practices amidst this rapidly evolving molecular diagnostic landscape.”