Chemotherapy-induced unconjugated hyperbilirubinemia caused by a mutation of the bilirubin uridine-5 '-diphosphate-glucuronosyltransferase gene

Chemotherapy for malignant neoplasms sometimes causes unconjugated hyperbil irubinemia in the absence of liver dysfunction. We analyzed the association of chemotherapy-induced hyperbilirubinemia with mutations of the bilirubin uridine-5'-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1) from tw o leukemic patients in whom chemotherapy resulted in a hyperbilirubinemic r esponse. We isolated genomic DNA from peripheral blood samples and amplifie d UGT1A1 by polymerase chain reaction. The amplified DNA fragments were ana lyzed by direct sequencing. The genes of the two patients revealed an ident ical heterozygous missense mutation in exon 1 (211G-->A: G71R). This UGT1A1 mutation may be the basis of chemotherapy-induced unconjugated hyperbiliru binemia.