UGT1A1
Overview
UGT1A1 (UDP Glucuronosyltransferase Family 1 Member A1) encodes the enzyme responsible for hepatic glucuronidation of SN-38, the active metabolite of the chemotherapeutic irinotecan. The UGT1A1*28 allele (homozygous (TA)7TAA promoter repeat) reduces enzyme activity, increasing SN-38 exposure and risk of severe irinotecan toxicity. Germline identification of this pharmacogenomic variant is clinically actionable.
Alterations observed in the corpus
- Homozygous UGT1A1*28 (TA)7TAA allele identified in two pediatric patients with pineoblastoma and hepatocellular carcinoma — pharmacogenomic flag for irinotecan/SN-38 toxicity; reported as a clinically impactful germline finding PMID:28007021
Cancer types (linked)
- PB (pineoblastoma): germline UGT1A1*28 homozygosity identified in a patient, with clinical implication for irinotecan dosing PMID:28007021
Co-occurrence and mutual exclusivity
- No co-mutation patterns reported in the corpus.
Therapeutic relevance
- Homozygous UGT1A1*28 predicts impaired SN-38 glucuronidation and elevated irinotecan toxicity; detection warrants dose reduction or avoidance of irinotecan-based regimens PMID:28007021
Open questions
- The clinical management protocol following UGT1A1*28 detection (dose reduction vs. alternative agent) was not specified in the reporting study.
Sources
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