Polymerase Chain Reaction (PCR) with capillary electrophoresis
Irinotecan, also known as Camptosar® or CPT-11, is an anti-neoplastic agent used to treat colorectal cancers. Uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) is responsible for the metabolic inactivation of SN-38 (active form of Irinotecan) via glucuronidation. Individuals with low levels of UGT1A1 activity are at increased risk for toxicity following Irinotecan administration, due to the presence of elevated levels of unconjugated SN-38. Decreased UGT1A1 activity can result from mutations in the coding sequence of the UGT1A1 gene, which alter the structure of the encoded protein, or from decreased expression of the normal protein product. A common cause of decreased expression levels of UGT1A1 is a variation in the number of TA repeats in the TATA box of the UGT1A1 gene promoter. The (TA)6 (i.e., 6 TA repeats) version of the promoter is considered to be the "normal" or wild type. Compared to the (TA)6 promoter, the (TA)7 version has a decreased activity, leading to the production of lower levels of UGT1A1 transcripts. To date, alleles containing 5, 6, 7, and 8 TA repeats have been identified. Several clinical studies have shown that individuals who are homozygous, and potentially those who are heterozygous, for the UGT1A1 (TA)7 promoter allele (UGT1A1*28) are at increased risk for the development of a significant adverse response to the standard dose of Irinotecan. Therefore, in July of 2005, the FDA altered the package labeling of Irinotecan to suggest a lower starting dose of Irinotecan for patients known to be homozygous for the UGT1A1 *28 (i.e., 7 TA repeat) allele.
Interpretive report provided.
This test does not detect or report alleles other than the (TA)5 (UGT1A1*36), (TA)6 (UGT1A1*1), (TA)7 (UGT1A1*28), and (TA)8 (UGT1A1*37). Numerous variants outside of the TA repeat region have been described that impair UGT1A1 activity. In addition, drug metabolism may be affected not only by other variants in the UGT1A1 gene, but also by other factors such as drug-drug interactions. Results should be interpreted in the context of clinical findings, family history, and other laboratory testing. A negative test result does not exclude risk for adverse drug reactions with UGT1A1-metabolized drugs or congenital unconjugated hyperbilirubinemia. If results do not match clinical findings, consider full gene sequencing of the UGT1A1 gene.
2 - 7 days
- Gilbert Syndrome
- Uridine Diphosphate Glucuronyltransferase 1A1 Promoter Genotyping
- UGT1A1 Promoter Genotyping PCR
- Irinotecan Sensitivity Analysis
Collect blood in a lavender top tube. Refrigerate and send intact blood or bone marrow specimen within 48 hours of collection.
By ordering this test the clinician acknowledges that informed consent has been obtained from the patient as required by applicable state or federal laws and the ordering clinician has authorization from the patient permitting MLabs to report the test results to the ordering clinician. Test includes pathologist interpretation of results billed as a separate additional charge. This test is not available without interpretation.