DPYD Sequencing Identifies More Clinically Relevant Variants as Compared to Targeted Genotyping

Analysis of 9 years of DPYD sequencing results, comparison of positive test rates between exhaustive sequencing and targeted genotyping strategies (AMP Tier 1/2 panels), quantification of rare variants missed by targeted approaches

A 9-year retrospective analysis of DPYD sequencing results compares diagnostic yield of exhaustive sequencing vs targeted genotyping strategies (AMP Tier 1 and 2 panels) for identifying patients at risk of severe fluoropyrimidine toxicity. Sequencing identifies significantly more clinically actionable pathogenic variants than targeted approaches, particularly rare variants with reduced functional activity (activity score <1) not covered by standard panels. These data support transitioning to DPYD sequencing as standard of care before all fluoropyrimidine treatments.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The targeted genotyping vs DPYD sequencing debate is central to clinical implementation: targeted panels are cheaper and faster, but miss rare variants that may represent a non-trivial fraction of at-risk patients. This 9-year study provides robust yield data justifying sequencing adoption, particularly in centers with high fluoropyrimidine prescription volumes.

Clinical impact: 3/3 · Evidence strength: 3/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 9/10