Characterization of a rare nonpathogenic sequence variant (c.1905C>T) of the dihydropyrimidine dehydrogenase gene (DPYD)

Background In the era of precision medicine, the suitability of fluoropyrimidine therapies in clinical oncology can be checked by pharmacogenetic investigations of single patients, thus optimizing resources and indicating the appropriate drugs to personalize their chemotherapy. For example, the presence of dihydropyrimidine dehydrogenase gene (DPYD) polymorphisms in cancer patients may lead to adverse effects when adopting fluoropyrimidine-based therapies. Methods We detected in a cancer patient a rare germline synonymous heterozygous variant of DPYD (c.1905C>T) in proximity to the exon 14 splice donor site. Because in silico analyses hypothesized potential deleterious effects of the splice site, we performed both quantitative and qualitative mRNA analyses to investigate the possible pathogenic nature of the variant. Results We did not detect any alterations in mRNA expression or in the cDNA sequence of DPYD gene transcript. Conclusions Our observations suggest that the c.1905C>T variant of DPYD does not have a pathogenic effect. Therefore, assessment of the clinical significance of rare sequence variants could emphasize the predictive value of DPYD gene alterations in identifying patients at potential risk for fluoropyrimidine-related toxicity.