Developing DPYD Genotyping Method for Personalized Fluoropyrimidines Therapy

Area of Science:

• Pharmacogenomics
• Molecular Diagnostics
• Oncology

Background:

• Fluoropyrimidine drugs are essential chemotherapy agents for solid tumors.
• Severe toxicity affects 10-40% of patients receiving fluoropyrimidine therapy.
• DPYD gene variants impairing dihydropyrimidine dehydrogenase activity increase toxicity risk.

Purpose of the Study:

• Develop a pharmacogenetic test to screen for DPYD variants.
• Identify patients at increased risk of fluoropyrimidine-induced toxicity.
• Guide personalized fluoropyrimidine therapy selection.

Main Methods:

• Developed a multiplex allele-specific polymerase chain reaction (AS-PCR) assay.
• Detected five common DPYD variants (c.557A > G, c.1129-5923C > G, c.1679T > G, c.1905 + 1G > A, c.2846A > T).
• Validated the assay using population and proficiency testing samples, confirmed by Sanger sequencing.

Main Results:

• Successfully detected DPYD variants in deidentified population and proficiency samples.
• Assay demonstrated high concordance with Sanger sequencing for all tested variants.
• Identified heterozygous carriers for key DPYD variants.

Conclusions:

• A robust multiplex AS-PCR assay for rapid DPYD variant detection was established.
• The test effectively screens for DPYD variants associated with fluoropyrimidine toxicity.
• This assay supports personalized medicine by identifying at-risk patients for safer chemotherapy.