Concordance of Blood-Based and Normal Tissue-Based Dihydropyrimidine Dehydrogenase (DPYD) Genotyping

Abstract

In response to the recently published article by Sharma et al, this letter to the editor presents data about the concordance of blood and normal tissue-based evaluation of DPYD genotyping that suggests that pharmacogenetic screening could be contextual to tumor molecular profiling.

In Reply

“…We agree with Dr. Morelli and colleagues 1 that logistical challenges are a significant obstacle to wider implementation of DPYD genotyping prior to fluoropyrimidine chemotherapy. We applaud these authors for this interesting demonstration that normal (non-malignant) tissue collected during biopsy or resection of cancer can be used as a DNA source for DPYD genotyping.…”

Pharmacogenomic-guided dosing of fluoropyrimidines beyond DPYD: time for a polygenic algorithm?

“…Therefore, we expect that different variants will be incorporated in a FP polygenic algorithm and that, in each case, the predictive value of the algorithm should be tested and validated within populations. Moreover, even though a 100% overall concordance has been shown for DPYD genotyping in blood and tissue samples ( Morelli et al, 2022 ), it should be considered that in tumor tissue genetic alterations are possible in other FP-associated genes that may affect tissue-specific FP catabolism and action. Additionally, the expression of genes regulating FP bioavailability can be influenced by transcriptional factors activated by the tumor-related characteristics ( Wu et al, 2016 ; Suenaga et al, 2021 ; Delhorme et al, 2022 ).…”