Robert J. Turesky, Ph.D., Arthur P. Grollman, M.D.
N.Y. State Department of Health Wadsworth Center, Stony Brook University School of Medicine
NIEHS Grants R01ES019564, P01ES004068
NIEHS grantees used genome-wide sequencing to identify a mutational signature of aristolochic acid that can link a person’s cancer with exposure to the environmental mutagen. The research shows that genome-wide sequencing can be used to detect whether a person was exposed to carcinogens.
Aristolochic acid is found in Aristolochia plants, which have been used for medicinal purposes for more than 2000 years. Recently, scientists discovered that consumption of the plants is associated with urothelial carcinoma of the upper urinary tract (UTUC). To determine the molecular signature of aristolochic acid in UTUC DNA, the researchers conducted exome sequencing of tumors from 19 individuals with documented exposure to aristolochic acid and seven patients with no known exposure.
The analysis revealed an average of 753 mutations in each tumor in the aristolochic acid group, with 72 percent of the mutations being A:T-to-T:A transversions. For comparison, they found 91 mutations in tumors from the non-exposed group. The A:T-to-T:A mutational signature showed up frequently in oncogenes and tumor suppressor genes in UTUC tumors associated with aristolochic acid. The investigators also detected the aristolochic acid mutational signature in one patient's tumor from a UTUC cohort without previous indication of aristolochic acid.
Citation: Hoang ML, Chen CH, Sidorenko VS, He J, Dickman KG, Yun BH, Moriya M, Niknafs N, Douville C, Karchin R, Turesky RJ, Pu YS, Vogelstein B, Papadopoulos N, Grollman AP, Kinzler KW, Rosenquist TA. 2013. Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing. Sci Transl Med 5(197):197ra102.