Diagnosis; Drug Response; Therapeutic management

Establish or confirm diagnosis

Guidance for selecting a drug therapy and/or dose

Individuals needing preemptive or reactive genotyping for pharmacogenomic purposes. Individuals with clinical features of dihydropyrimidine dehydrogenase deficiency.

Is research allowed on the sample after clinical testing is complete? Help
Research testing is only performed under IRB approved protocol with an opt-out policy in place.

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 … 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23 exons of the DPYD gene (using gene transcript NM_000110.3) using mutation detection software and visual inspection.(Unpublished Mayo method) View more

Positive results are confirmed when appropriate.

Tests performed
Entire test performed in-house

Accuracy and analytical sensitivity for simple variants (SNVs and INDELs): (>99%).

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 … 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. View more

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP

Software used to interpret novel variations Help
Variants may be analyzed using any combination of the following: Alamut, REVEL, Polyphen-2, SIFT, AGVGD, MutationTaster, SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, SpliceAI, gene-specific online databases, ISCA, UCSC Genome Browser

Laboratory's policy on reporting novel variations Help
All novel variants and copy number variants are evaluated for potential pathogenicity and included in the written report, accordingly.