Cancer genomics of aristolochic acid induced urinary tract carcinoma
Rosenquist, Sidorenko, Dickman
The TP53 tumor suppressor gene in AA-induced urothelial tumors has an abnormally high rate of A-to-T mutations located primarily on the non-transcribed strand of DNA (Moriya, et al. 2011). We are now collaborating with Drs. Vogelstein and Kinzler of Johns Hopkins University to sequence the whole exome of DNA obtained from urothelial cancer and matching normal tissue from Taiwanese patients exposed to AA. This study should allow us to establish the genome-wide mutational signature of AA and to identify driver mutations underlying upper urothelial carcinogenesis. Identifying the driver genes in UUC combined with the unique AA-mutation spectrum may yield tools for early detection of this tumor in at risk populations. Also we hope to gain insight into several open questions such as why only a subset of persons exposed to AA develops tumors. Also, although AA-DNA adducts accumulate to high levels in several tissues why do tumors develop only in the upper urinary tract?
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