Genotyping NUDT15, TPMT and CEP72
Overview of the test
RPRD™ Diagnostics (RPRD) introduces the CNT (CEP72, NUDT15 and TPMT) and NT panels (NUDT15 and TPMT), investigating all clinically relevant genetic variants of these important PGx genes in a single test. Compared to testing only a limited number of variants, RPRD’s comprehensive panels yield thorough dosing guidelines for thiopurines and vincristine with higher accuracy.
Clinical Value
The tests provides clinically relevant information to help clinicians determine effective therapies and dosing for patients with acute lymphoblastic leukemia (ALL) or inflammatory bowel disease (IBD).
TPMT and NUDT15 are two important PGx genes recommended in the latest CPIC guidelines to guide proper dosing of thiopurines, including azathioprine, mercaptopurine, and thioguanine. Thiopurines are commonly used drugs to treat acute lymphoblastic leukemia (ALL), autoimmune diseases, and inflammatory bowel disease (IBD), or to prevent rejection after organ transplant.1 Variants in TPMT and NUDT15 are associated with increased risk of life-threatening myelosuppression induced by thiopurines.1,2,3
Whereas TPMT variants are primarily found in those of European descent, genetic variants in NUDT15 are found in many populations (Figure 1).2
One genetic variant of CEP72 has been associated with vincristine-related peripheral neuropathy. Thus, genotyping of CEP72 is recommended to guide safer dosing of vincristine.4
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Learn how TPMT and NUDT15 PGx reduces thiopurines-related ADRs.
KEY ADVANTAGES
Covers CPIC guideline-recommended genes in one test
Analyze both CPIC guideline-recommended genes, TPMT and NUDT15, for thiopurines in a single test.
Test all clinically relevant variants
Test all clinically relevant variants of TPMT, NUDT15, and CEP72 to enhance accuracy and eliminate guesswork.
Rapid turnaround time (TAT)
Highly accurate clinical results are delivered within 3-5 days to support potentially life-saving clinical decision making.
NT Panel CNT Panel Genes Alleles Detected by Genotyping Assay Drugs Indications
X X TPMT *1, *2, *3A, *3B, *3C, *4, *8, *24 Thiopurines Acute Lymphoblastic Leukemia,
Inflammatory Bowel Disease,
Autoimmune Diseases,
Organ Transplant
X X NUDT15 *1, *2, *3, *4, *5, *6, *7, *8, *9
X CEP72 SNP rs924607: C, SNP rs924607: T Vincristine Acute Lymphoblastic Leukemia
Testing for individual gene (NUDT15, CEP72 or TPMT) is also available. Contact us for more information.
Gene Details
NUDT15
Download NUDT15 Spec Sheet
NUDT15 encodes an enzyme (nudix hydrolase) which is a negative regulator of thiopurines (e.g., 6-mercaptopurine, azathioprine, thioguanine, etc.) activation and toxicity. Genetic variants in the NUDT15 gene can modulate enzymatic activity and the metabolism of thiopurines.1,2,3
Pharmacogenetic testing for these variants can identify individuals who may fail to respond to standard dosages of drugs metabolized by NUDT15 or be at an increased risk of adverse drug reactions.
The latest CPIC guidelines recommend testing for NUDT15 and TPMT to guide the dosing of thiopurines. Read more.
A recent landmark study shows NUDT15 variants are associated with thiopurine-induced myelosuppression in patients with IBD. Read more.
Single gene testing for NUDT15 is also available. Please contact us for more information.
TPMT
Download TPMT Spec Sheet
TPMT encodes an enzyme that is a negative regulator of thiopurines (e.g., 6-mercaptopurine, azathioprine, thioguanine, etc.) activity. Genetic variants of the TPMT gene can modify enzymatic activity and the ability to metabolize thiopurines.1 Pharmacogenetic testing for these variants can identify individuals who may have an increased risk of having adverse drug reactions or may fail to respond to standard dosages of drugs metabolized by TPMT.
The latest CPIC guidelines recommend testing for NUDT15 and TPMT to guide the dosing of thiopurine. Read more.
CEP72
Download CEP72 Spec Sheet
CEP72 encodes a protein that is essential for microtubule formation. The chemotherapeutic drug vincristine exerts its cytotoxic effects by interfering with microtubule formation and mitotic spindle dynamics, leading to mitotic arrest and cell death. One specific sequence variant in CEP72 (T/T genotype) is associated with an increased risk and severity of vincristine-related peripheral neuropathy in individuals ALL.4
REFERENCES
- Relling MV, et al. CPIC Guideline for Thiopurines and TPMT and NUDT15. Clin Pharmacol Ther. 2019 May;105(5):1095-1105.
- Moriyama T, et al. NUDT15 Polymorphisms Alter Thiopurine Metabolism and Hematopoietic Toxicity. Nat Genet. 2016 Apr;48(4):367-73.
- Schaeffeler, E. et al. Impact of NUDT15 Genetics on Severe Thiopurine-related Hematotoxicity in Patients with European Ancestry. Genetics in Medicine. Feb 2019. [Ahead of ePub].
- Stock W, et al. Clin Pharmacol Ther. 2017;101(3):391-95.
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