Non-invasive detection of mutagenic exposure to aristolochic acid using ultra-deep sequencing of blood and urine samples

Aristolochic acids (AAs) are potent nephrotoxins and carcinogens found in certain herbal remedies, driving a high burden of urothelial and liver malignancies globally. Currently, at a genomic level, AA exposure is detected retrospectively via DNA sequencing of clonal tumors, which limits opportunities to detect the mutational imprints of the exposure before tumor formation, when risk stratification may be possible. In a cohort of 12 urothelial carcinoma of the urinary tract patients, we profiled matched tumor and normal tissues alongside peripheral blood, urine sediments, and sorted leukocyte

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