Characterization of Reference Materials for DPYD: A GeT-RM Collaborative Project.

Area of Science:

• Genetics
• Pharmacology
• Clinical Diagnostics

Background:

• The DPYD gene encodes dihydropyrimidine dehydrogenase (DPD), an enzyme critical for metabolizing the chemotherapy drug 5-fluorouracil (5-FU).
• Reduced DPD activity leads to severe, potentially fatal, adverse drug reactions in patients treated with 5-FU.
• A lack of standardized quality control materials hinders accurate DPYD pharmacogenetic testing.

Purpose of the Study:

• To address the need for quality control materials in DPYD pharmacogenetic testing.
• To characterize 33 DNA samples for DPYD variants to support clinical laboratory quality assurance.

Main Methods:

• Characterization of 33 DNA samples from Coriell cell lines for DPYD variants.
• Distribution of samples to four volunteer laboratories for genetic testing.
• Utilized Sanger sequencing and whole-genome sequence data from the 1000 Genomes Project for genotype determination.

Main Results:

• Identification of 33 distinct DPYD variants across the 33 characterized DNA samples.
• Successful distribution and testing of materials across multiple laboratories using diverse methods.

Conclusions:

• Well-characterized, publicly available DNA reference materials for DPYD are now available.
• These materials will enhance quality assurance and quality control in clinical pharmacogenetic testing laboratories.
• Supports the safe and effective use of 5-FU in cancer treatment through improved DPYD testing.