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Test Name:
5-Fluorouracil Sensitivity (DPYD, TYMS and MTHFR), 8 Mutations

• SBMF No:
  44967
• Performance Lab Name:
  ARUP Laboratories
• Test Mnemonic:
  5-FU
• ABN:
  Required – Not FDA-Approved
• CPT Code:
  83891; 83900; 83901x5; 83912; 83914x16
• Ref Lab Test No:
  2002420
• Also Known As:
  5 Fluorouracil
  5-FU
  5FU
• Spec Type:
  Whole blood
• Spec Container:
  Lavender top (EDTA) or Pale Yellow top (ACD-A or B) tube
• Pref Vol:
  3.0 mL
• Min Vol:
  1.0 mL
• Fasting:
  No
• Patient Prep:
  Counseling and informed consent are recommended for genetic testing
  Form required:
  Informed Consent for Molecular Genetic Testing
• Spec Collect:
  Routine venipuncture
• Spec Process:
  Gently invert tube to mix blood with the anticoagulant
  Do not centrifuge
  Do not remove plasma from cells
  Forward entire tube of unprocessed whole blood to the laboratory
• Spec Store Transport:
  Refrigerated
• Spec Stability:
  3 days room temperature (20-30°C)
  1 week refrigerated (2-8°C)
  Frozen (-20°C): Unacceptable
• Spec Reject:
  Frozen specimen
• Methodology:
  Polymerase Chain Reaction (PCR)
  Primer Extension
• Clinical Significance:
  Refer to:
  
• Reference Range:
  

  By report

  Interpretive Data:
  Background information for 5-Fluorouracil Sensitivity Through Genotyping (DPYD, TYMS and MTHFR) 8 Mutations
  Characteristics: 5-fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs in the treatment of colorectal and other solid tumors. Adverse effects of 5-FU therapy, such as mucositis, neutropenia, nausea, diarrhea and neurological symptoms, occur in up to 15 percent of patients treated. Mutations in genes involved in 5-FU metabolism and response, including dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS) and methylenetetrahydrofolate reductase (MTHFR), may be associated with 5-FU toxicity and/or altered response. 5-FU drug metabolism, efficacy, and risk for toxicity may be affected by genetic and non-genetic factors not detected by this assay. Genotyping does not replace the need for therapeutic drug or other clinical monitoring. For 5-FU Metabolism, refer to table below.
  Prevalence: Population estimates for heterozygosity and homozygosity for DPYD alleles with impaired function are 3-5 percent and 0.1 percent, respectively. Heterozygosity for 1494 del TTAAAG (6 bp deletion) in TYMS occurs in 50 percent of Caucasians, 7 percent are homozygous. U.S. allele frequencies for MTHFR c.677C>T and c.1298A>C are 39 percent and 17 percent, respectively.
  Cause: Deleterious mutations in genes involved with metabolism of and response to 5-FU including DPYD, TYMS and MTHFR.
  Mutations Tested: Refer to table below.
  Clinical Sensitivity & Specificity: Unknown.
  Methodology: PCR and Detection Primer Extension.
  Analytical Sensitivity and Specificity: 99 percent.
  Limitations: Only the targeted DPYD, TYMS and MTHFR mutations will be detected. Rare diagnostic errors may occur due to primer site mutation.

       5-FU Metabolism

  Gene name	Protein name	Normal protein function
  DPYD	DPD	Inactivates approximately 80 percent of administered 5-FU
  TYMS	TS	Primary drug target of 5-FU; complexes with an activated 5-FU metabolite resulting in suppression of DNA synthesis
  MTHFR	MTHFR	Metabolizes folate to produce an activated co-factor needed for TS; impairment increases rate of activity of TS

       Mutations Tested

  Gene	Variant	Variant Common Name	Predicted Consequence
  DYPD         TYMS MTHFR	IVS14+1G>A      c.85T>C c.1679T>G c.-1590T>C c.2846A>T rs16430 c.677C>T c.1298A>C	*2 *9A *13     1494 del TTAAAG C677T A1298C	Abolished DPD activity Reduced DPD activity Reduced DPD activity Reduced DPD activity Reduced DPD activity Reduced TS expression Reduced MTHFR activity Reduced MTHFR activity

• Additional Test Info:
  

  Genetic Compliance Statement:
  The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing.

  Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

• Day Run:
  Mon, Thu
• Time Reported:
  8-15 days
• Test Type:
  GENETIC