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Test Code DPYDG Dihydropyrimidine Dehydrogenase (DPYD) Full Gene Sequencing

Secondary ID

65213

Useful For

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

 

For an individual with suspected dihydropyrimidine dehydrogenase (DPD) deficiency, this test may be useful in identifying variants associated with decreased or absent DPD enzyme activity

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reporting Name

DPYD Full Gene Sequencing

Specimen Type

Varies


Advisory Information


 



Specimen Required


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)/Refrigerated

 

Supplies: DNA Saliva Collection Kit (T651)

Specimen Type: Saliva

Container/Tube: Oragene DNA Self-Collection Kit (T651: fees apply)

Specimen Volume: Full tube

Collection Instructions:

1. Fill tube to line.

2. Send specimen in original container per kit instructions.

Specimen Stability Information: Ambient

 

Specimen Type: 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


Specimen Minimum Volume

Blood: 0.45 mL; Saliva: Full tube of saliva

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Reject Due To

Hemolysis

NA

Lipemia

NA

Icterus

NA

Other

NA

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 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 mental retardation.

 

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

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.

 

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

Clinical Reference

1. Online Mendelian Inheritance in Man: Dihydropyrimidine dehydrogenase deficiency. #274270. Updated 4/18/2012. Available from http://omim.org/

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. FDA Table of Pharmacogenomic Biomarkers in Drug Labeling. Available at: http://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

Day(s) and Time(s) Performed

Varies; 8 a.m.

Analytic Time

5 days (Not reported on Saturday or Sunday)

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

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 U.S. Food and Drug Administration.

CPT Code Information

81479

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DPYDG DPYD Full Gene Sequencing In Process

 

Result ID Test Result Name Result LOINC Value
48263 DPYD Predicted Toxicity Risk In Process
48264 Result Details In Process
48268 Interpretation In Process
48266 Method In Process
48269 Disclaimer 62364-5
48270 Reviewed by In Process
92011 Additional Information 48767-8

Forms

New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.