Test Catalog

Test Id : DPYDG

Dihydropyrimidine Dehydrogenase, DPYD Full Gene Sequencing, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying individuals at increased risk of toxicity when considering 5-fluorouracil and capecitabine chemotherapy treatment

 

May be useful in identifying variants associated with decreased or absent dihydropyrimidine dehydrogenase enzyme activity for an individual with this deficiency suspected

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

DPYD Full Gene Sequencing

Aliases
Lists additional common names for a test, as an aid in searching

5-Fluorouracil

5-FU

Capecitabine

DPD

DPYD

Specimen Type
Describes the specimen type validated for testing

Varies

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Multiple whole blood EDTA genotype tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.

 

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 specimen in original tube.

Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days

 

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

 

Specimen Type: Extracted DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 250 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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) form with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 0.45 mL

Saliva: 1 swab

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying individuals at increased risk of toxicity when considering 5-fluorouracil and capecitabine chemotherapy treatment

 

May be useful in identifying variants associated with decreased or absent dihydropyrimidine dehydrogenase enzyme activity for an individual with this deficiency suspected

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 dihydropyrimidine dehydrogenase (DPYD) gene encodes the rate-limiting enzyme for fluoropyrimidine catabolism and eliminates over 80% of administered 5-FU. Dihydropyrimidine dehydrogenase (DPYD) activity is subject to wide variability, mainly due to genetic variation (table 1). This results in a broad range of enzymatic deficiency from partial (3%-5% of population) to complete loss (0.2% of population) of enzyme activity.(2,3) Patients who are deficient in DPYD are at an increased risk for side effects and toxicity when undergoing 5-FU treatment.(4) In addition, pathogenic homozygous or compound heterozygous variants within DPYD are associated with dihydropyrimidine dehydrogenase (DPD) deficiency. DPD deficiency shows large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and intellectual disabilities.

 

Table 1. Known Genetic Variations Associated with Fluoropyrimidine Treatment

Gene

cDNA numbering

Alternative name

Enzyme activity

Phenotype

DPYD

No variations identified

*1

 

 

c.1905+1G->A

*2A

No activity or significantly reduced activity

High risk for fluoropyrimidine toxicity

c.1679T->G

*13

c.1898delC

*3

c.299_302delTCAT

*7

c.1156G->T

*12

c.2846A->T

rs67376798

Reduced activity

Increased risk for fluoropyrimidine toxicity

c.1129-5923C->G

rs75017182

c.703C->T

*8

Probable reduced function

Increased risk for fluoropyrimidine toxicity

c.2983G->T

*10

c.1003G->T

*11

c.557A->G

rs115232898

c.1601C->T

*4

Normal activity**

Normal risk for fluoropyrimidine toxicity

c.1627A->G

*5

c.2194C->T

*6

c.85T->C

*9A

*Other or novel variations, besides those listed here, may also impact fluoropyrimidine-related side effects and tumor response and will be reported if detected.

**Alleles that are categorized as having normal enzyme activity (eg, *4, *5, *6, *9A) will not be reported if detected because variants with normal enzyme activity are not expected to impact fluoropyrimidine-related side effects and tumor response.

 

The DPYD gene is located on chromosome 1 and contains 2 transcripts. The longer transcript (NM_000110.3) contains 23 exons, and the shorter transcript (NM_001160301.1) contains 6 exons, with exon 6 being unique to this transcript. All exons from the longer transcript (NM_000110.3) and exon-intron boundaries are assessed.

 

Genetic variations involved in the metabolic pathway of fluoropyrimidines have been shown to contribute to the differences in clinical outcomes including toxicity and tumor response.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

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.

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic blood or marrow transplantation, a pretransplant DNA specimen is recommended for testing.

 

Dihydropyrimidine dehydrogenase (DPYD) genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's DPYD status.

 

Rare genetic variants exist that could lead to false-negative or false-positive results. Other variants in the primer binding regions can affect the testing, and ultimately, the genotype assessment made.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Large deletions or rearrangements are not detected by this assay, and these may affect DPYD protein expression and their impact on fluoropyrimidine related side effects and tumor response.

 

Sometimes a genetic alteration of unknown significance may be identified. In this case, testing of appropriate family members may be useful to determine pathogenicity of the alteration.

 

This test is not designed to provide specific dosing or drug selection recommendations and is to be used as an aid to clinical decision making only. Drug-label guidance should be used when dosing patients with medications regardless of the predicted phenotype.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. OMIM: 274270 Dihydropyrimidine dehydrogenase deficiency.. Johns Hopkins University; 1986. Updated April 18, 2012. Accessed December 4, 2020. Available from https://www.omim.org/entry/274270

2. Caudle KE, Thorn CF, Klein TE, et al: Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. 2013;94(6):640-645

3. Morel A, Boisdron-Celle M, Fey L, et al: Clinical relevance of different dihyropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther. 2006 Nov;5(11):2895-2904

4. U.S. Food and Drug Administration (FDA): Table of Pharmacogenomic Biomarkers in Drug Labeling. FDA; Updated June 2020, Accessed December 4, 2020. Available at: www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm

5. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424

6. Offer SM, Fossum CC, Wegner NJ, et al: Comparative functional analysis of DPYD variants of potential clinical relevance to dihydropyrimidine dehydrogenase activity. Cancer Res. 2014;74(9):2545-2554

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Genomic DNA is extracted from whole blood. The dihydropyrimidine dehydrogenase (DPYD) 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 the exons and intron/exon boundaries of all 23 exons of the DPYD gene (using gene transcript NM_000110.3) using mutation detection software and visual inspection.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

5 to 10 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood/Saliva: 2 weeks; Extracted DNA: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81232

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
DPYDG DPYD Full Gene Sequencing 94198-9
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
48263 DPYD Predicted Toxicity Risk 83009-1
48264 Result Details 82939-0
48268 Interpretation 69047-9
48266 Method 85069-3
48269 Disclaimer 62364-5
48270 Reviewed by 18771-6
92011 Additional Information 48767-8

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports