Oncology DPYD Genetic Testing Panel | Personalized Genetic Testing

ONCOLOGY PANEL
Genetic Testing for Personalized Cancer Medicine

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Personalized Genetic Testing provides an invaluable service to physicians and patients throughout the U.S.

Thousands of Tests Performed

Providing doctors with the information needed to determine the best medicines and treatments for each of their patients.

20+ Years Experience

Experience in biotechnology, pharmaceutical, hematology, flow cytometry, clinical molecular biology, immunology, and chemistry industries.

Fast 5-Day Turnaround

Using the latest technologies from the leaders in the industry, our process is 3 times faster than competitor’s analysis methods.

Accurate Reporting

Through Coriell Institute, backed by over 60 years of research experience providing the quality control required for validation in pharmacogenetics testing.

The PGT Oncology Panel supports doctors in determining precision cancer medicine treatments that are best suited for a patient’s genetic profile.

PGT Oncology Panel provides genetic results for:

TPMT

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP), thioguanine and azathioprine (AZA). These drugs are used to treat conditions such as acute lymphoblastic leukemia, inflammatory bowel disease, rheumatoid arthritis, and organ transplant rejection. Thiopurine methyltransferase (TPMT) is a phase two drug-metabolizing enzyme expressed in the kidney, red blood cells, liver and other tissues. Measurement of TPMT activity can predict thiopurine-induced myelosuppression, which can be life-threatening. It was found that the risk of myelosuppression was 4.5-fold higher when TPMT activity was low vs normal in patients with inflammatory bowel disease (Crohn’s disease or ulcerative colitis). TPMT methylates and inactivates mercaptopurine.

The approximately 10% of populations that inherit intermediate or absent TPMT activity is at higher risk of myelosuppression and its attendant toxicity if prescribed “normal” doses of thiopurines; in addition, such patients appear at higher risk of secondary cancers. Individuals with diminished TPMT activity may necessitate thiopurine dosage reductions of 50 to 90 percent to tolerate therapy and reduce the risk of adverse reactions.

Drugs related: Mercaptopurine (Purinethol®), Thioguanine (Tabloid®), Azathioprine (Imuran).

DPYD

The DPYD gene encodes an enzyme known as dihydropyridine dehydrogenase (DPYD), which is dangerous to the metabolism of fluoropyrimidine drugs, such as 5-FU and capecitabine. It is also the rate-limiting step in the breakdown of pyrimidines, such as uracil and thymine. Mutations in DPYD are known to cause severe 5-FU toxicity as a result of decreased DPYD activity.

DPYD lab testing has identified more than 50 mutations in the DPYD gene in people with dihydropyridine dehydrogenase deficiency. DPYD gene testing can identify the mutations that interfere with the breakdown of uracil and thymine and result in excess quantities of these molecules in the blood, urine, and the fluid that surrounds the brain and spinal cord (cerebrospinal fluid).

Mutations in the DPYD gene also interfere with the breakdown of drugs with structures similar to the pyrimidines, such as the cancer drugs 5-fluorouracil and capecitabine. As a result, these drugs accumulate in the body and cause the severe reactions that can occur in people with dihydropyridine dehydrogenase deficiency. DPYD genetic testing can assist physicians in determining personalized medicine cancer treatment.

Drugs related: Capecitabine (Xeloda®), Fluorouracil (Carac®), Pyrimidinedione (Tegafur®)

CYP2D6

The CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, and is one of the main enzymes responsible for converting tamoxifen into its major active metabolite, endofixen. Variants in the CYP2D6 allele may lead to reduced (“intermediate metabolizer”) or absent (“poor metabolizer”) enzyme activity. Individuals who carry these variant alleles may have reduced plasma concentrations of endoxifen and benefit less from tamoxifen therapy.

Drugs Related: Tamoxifen

CYP3A4

CYP3A4 is responsible for the metabolism of approximately 50-60% of clinical drugs used today, including acetaminophen, codeine, cyclosporine, diazepam, and erythromycin. It is important for the metabolism of steroid hormones.

Detecting variants of the CYP3A4 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard dosages of 3A4 substrates. Roughly 4-10% of the general population possesses inherited differences in 3A4 that cause decreased metabolism. These Decreased Metabolizers may be at increased risk for dose-dependent side effects to drugs normally inactivated by 3A4.

Drugs related: Cabazitaxel (Jevtana®), Gefitinib (Iressa®), Ruxolitinib (Jakavi®), Sunitinib (Sutent®).

ABCB1

ABC transporters form one of the largest of all protein families and are central to many important biomedical phenomena, including the resistance of cancers and pathogenic microbes to drugs.

Drugs related: Fluorouracil (Carac®), Methotrexate (Trexall®), Vincristine (Marqibo®), Ondansetron (Zofran®), Dexamethasone (Maxidex®), Doxorubicin (Doxil®)

 UGT1A1

Mutations in the UGT1A1 gene that cause syndrome result in reduced or absent function of the bilirubin-UGT enzyme. People with Crigler-Najjar syndrome type 1 (CN1) have no enzyme function, while people with Crigler-Najjar syndrome type 2 (CN2) have less than 20 percent of normal function. The signs and symptoms of CN1 are more severe than those of CN2. The loss of bilirubin-UGT function decreases glucuronidation of unconjugated bilirubin. This toxic substance then builds up in the body, causing hyperbilirubinemia, jaundice, and sometimes, kernicterus.

Drugs related: Nilotinib (Tasigna®), Erlotinib (Tarceva®), Pazopanib (Votrient®)

PGT Oncology Panel can help define the appropriateness and dosage of many of these prescribed drugs including:
Therapeutic Class Name of Drug

Antineoplastic Agents

Cabazitaxel (Jevtana®)
Capecitabine (Xeloda®)
Carboplatin (Paraplatin®)
Cyclophosphamide (Endoxan®)
Cisplatin (Platinol®)
Dexamethasone (Maxidex®)
Fluorouracil (Carac®)
Methotrexate (Trexall®)
Pemetrexed (Alimta®)
Oxaliplatin (Eloxatin®)
Docetaxel (Taxotere®)
Paclitaxel (Abraxane®)
Estrogen Antagonists Tamoxifen (Soltamox®)
Kinase Inhibitors Erlotinib (Tarceva®)
Gefitinib (Iressa®)
Nilotinib (Tasigna®)
Pazopanib (Votrient®)
Ruxolitinib (Jakavi®)
Sunitinib (Sutent®)
Topoisomerase I Inhibitors Irinotecan (Camptosar®)