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Test ID: DPYDG Dihydropyrimidine Dehydrogenase, DPYD Full Gene Sequencing, Varies

Useful For

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

Method Name

Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis

Reporting Name

DPYD Full Gene Sequencing

Specimen Type

Varies


Ordering Guidance


 



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) 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


Specimen Minimum Volume

Blood: 0.45 mL
Saliva: 1 swab

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

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 Pharmacogenomic 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. 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

Day(s) Performed

Varies

Report Available

5 to 10 days

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

81232

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DPYDG DPYD Full Gene Sequencing 94198-9

 

Result ID Test Result Name Result LOINC Value
48263 DPYD Predicted Toxicity Risk 83009-1
48264 Result Details 82939-0
48268 Interpretation 69047-9
48266 Method 49549-9
48269 Disclaimer 62364-5
48270 Reviewed by 18771-6
92011 Additional Information 48767-8

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.

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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