Home
HelpTest Code DPYDZ Dihydropyrimidine Dehydrogenase, DPYD Full Gene Sequencing, Varies
Ordering Guidance
This test and DPYDQ / Dihydropyrimidine Dehydrogenase Genotype, Varies are both used to test for genetic variants in the DPYD gene that are associated with fluoropyrimidine toxicity. This test can detect rare variants in addition to common variants and is the appropriate test for diagnosis of dihydropyrimidine dehydrogenase deficiency. Additionally, this test is expected to have an overall higher detection rate than DPYDQ, particularly for individuals of non-European ancestry.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days
Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 Swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient 30 days
Additional Information: Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.
Secondary ID
610051Useful For
Identifying individuals at increased risk of toxicity when considering 5-fluorouracil and capecitabine chemotherapy treatment
Identifying common and rare variants associated with decreased or absent dihydropyrimidine dehydrogenase (DPD) enzyme activity in individuals with suspected DPD deficiency
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis
Reporting Name
DPYD Full Gene Sequencing, VSpecimen Type
VariesSpecimen Minimum Volume
Blood: 0.45 mL; Saliva: See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
5-Fluorouracil (5-FU) and its orally administered prodrug, capecitabine, are fluoropyrimidine-based chemotherapeutic agents that are widely used for the treatment of colorectal cancer and other solid tumors.
The DPYD gene encodes dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme for fluoropyrimidine catabolism, which eliminates over 80% of administered 5-FU. Genetic variation in DYPD is the main cause for variability in DPD activity and can lead to partial or complete enzymatic deficiency (3-5% or 0.2% of the population, respectively).(2,3) Patients who are deficient in DPD are at an increased risk for adverse effects and toxicity when undergoing 5-FU treatment.(4) In addition, disease-causing homozygous or compound heterozygous variants within DPYD are associated with DPD deficiency. DPD deficiency shows a wide range of severity, from asymptomatic (albeit at risk for drug toxicity) to neurological problems, including seizures and intellectual disability, delayed motor development, and microcephaly.
DPYD variants impacting the metabolic pathway of fluoropyrimidines have been shown to contribute to the differences in clinical outcomes, including toxicity and tumor response. Common DPYD variants that result in no activity include c.1905+1G>A (*2A), c.299_302del (*7), c.703C>T (*8), c.2983G>T (*10), and c.1679T>G (*13). Common DPYD variants resulting in reduced activity include c.2846A>T (rs67376798), c.1129-5923C>G (rs75017182, also part of the HapB3 haplotype), and c.557A>G (rs115232898). In addition to these common variants, this sequencing test may also detect rare variants that impact DPD activity.
Reference Values
DPYD Total Activity Score: 2
DPYD Phenotype: Normal metabolizer
An interpretive report will be provided.
Interpretation
Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics recommendations as a guideline.(5) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Additionally variant functional status and activity score are assigned using the most recent published Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations as a guideline.(2)
For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Association Tables. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Method Description
Genomic DNA is extracted from whole blood or saliva. The DPYD (NM_000110.3) gene is amplified by polymerase chain reaction (PCR). The PCR products are then purified and sequenced in both directions using fluorescent dye-terminator chemistry. Sequencing products are separated on an automated sequencer and trace files analyzed for variations in all exons and intron/exon boundaries, plus the deeply intronic variant c.1129-5923C>G (rs75017182), using mutation detection software and visual inspection.(Unpublished Mayo method)
Day(s) Performed
Monday through Friday
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81232
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| DPYDZ | DPYD Full Gene Sequencing, V | 94198-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 618600 | DPYD Total Activity Score | In Process |
| 618601 | DPYD Phenotype | 79719-1 |
| 618602 | Result Details | 82939-0 |
| 618603 | Interpretation | 69047-9 |
| 618604 | Method | 85069-3 |
| 618605 | Disclaimer | 62364-5 |
| 618606 | Additional Information | 48767-8 |
| 618607 | Reviewed by | 18771-6 |