NEW YORK – The Association for Molecular Pathology on Monday released a report providing recommendations to help standardize the design and validation of clinical DPYD genotyping assays.
The recommendations are a joint consensus from AMP, the American College of Medical Genetics and Genomics (ACMG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the College of American Pathologists (CAP), the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Pharmacists Association, the European Society for Pharmacogenomics and Personalized Therapy (ESPT), the Pharmacogenomics Knowledgebase (PharmGKB), and the Pharmacogene Variation Consortium (PharmVar).
The report is intended to ensure that appropriate variants are included in clinical pharmacogenomic DPYD assays and was developed by the AMP Clinical Practice Committee's Pharmacogenomics Working Group. DPYD genotyping can help identify patients who might be at increased risk for severe fluoropyrimidine-related toxicity, Victoria Pratt, co-chair of the working group, said in a statement.
The group used a two-tier categorization of variants recommended for inclusion, which it has also done with previous clinical PGx genotyping assay recommendations, AMP said. Tier 1 recommended variants were chosen because they "have a well-characterized effect on functional activity of the protein and/or gene expression, have an appreciable minor allele frequency in a population/ancestral group, have available reference materials for assay validation, and are technically feasible for clinical laboratories to interrogate using standard molecular testing methods," the organization said.
Tier 2 optional variants, meantime, meet at least one but not all of the Tier 1 criteria. The recommendations do not include variants with an unknown effect on protein function or gene expression and are meant to be a reference guide, not a restrictive list, AMP noted.
The working group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations, the organization said in the report.