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

Area of Science:

• Pharmacogenomics
• Clinical Oncology
• Molecular Diagnostics

Background:

• Precision medicine utilizes pharmacogenetics to personalize chemotherapy, optimizing drug selection and resource allocation.
• Dihydropyrimidine dehydrogenase gene (DPYD) polymorphisms can cause adverse effects in patients undergoing fluoropyrimidine-based therapies.
• Investigating DPYD variants is crucial for predicting patient response and toxicity to chemotherapy.

Observation:

• A rare heterozygous synonymous variant (c.1905C>T) in the DPYD gene was identified near the exon 14 splice donor site in a cancer patient.
• In silico analyses suggested potential deleterious effects of the splice site variant.
• Quantitative and qualitative mRNA analyses were performed to assess the variant's pathogenicity.

Findings:

• No alterations in mRNA expression were detected for the DPYD gene transcript.
• No changes in the cDNA sequence of the DPYD gene transcript were observed.
• The c.1905C>T variant did not demonstrate a pathogenic effect on DPYD gene expression or sequence.

Implications:

• The DPYD c.1905C>T variant is unlikely to be pathogenic, suggesting it does not confer risk for fluoropyrimidine-related toxicity.
• Accurate assessment of rare DPYD variants is essential for predicting patient risk and guiding personalized cancer treatment.
• Further evaluation of DPYD gene alterations can enhance the predictive value for identifying patients susceptible to chemotherapy side effects.