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Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing.
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- Additional Information
- Source:
Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE
- Publication Information:
Original Publication: Washington, DC : American Association for the Advancement of Science
- Subject Terms:
- Abstract:
In humans, exposure to aristolochic acid (AA) is associated with urothelial carcinoma of the upper urinary tract (UTUC). Exome sequencing of UTUCs from 19 individuals with documented exposure to AA revealed a remarkably large number of somatic mutations and an unusual mutational signature attributable to AA. Most of the mutations (72%) in these tumors were A:T-to-T:A transversions, located predominantly on the nontranscribed strand, with a strong preference for deoxyadenosine in a consensus sequence (T/CAG). This trinucleotide motif overlaps the canonical splice acceptor site, possibly accounting for the excess of splice site mutations observed in these tumors. The AA mutational fingerprint was found frequently in oncogenes and tumor suppressor genes in AA-associated UTUC. The AA mutational signature was observed in one patient's tumor from a UTUC cohort without previous indication of AA exposure. Together, these results directly link an established environmental mutagen to cancer through genome-wide sequencing and highlight its power to reveal individual exposure to carcinogens.
- Comments:
Comment in: Sci Transl Med. 2013 Aug 7;5(197):197fs31. doi: 10.1126/scitranslmed.3006810. (PMID: 23926198)
Comment in: Nat Rev Urol. 2013 Oct;10(10):552. doi: 10.1038/nrurol.2013.186. (PMID: 23979661)
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- Grant Information:
CA57345 United States CA NCI NIH HHS; ES019564 United States ES NIEHS NIH HHS; P50 CA062924 United States CA NCI NIH HHS; ES004068 United States ES NIEHS NIH HHS; R37 CA057345 United States CA NCI NIH HHS; P01 ES004068 United States ES NIEHS NIH HHS; R01 CA057345 United States CA NCI NIH HHS; R01 ES019564 United States ES NIEHS NIH HHS
- Accession Number:
0 (Aristolochic Acids)
94218WFP5T (aristolochic acid I)
- Publication Date:
Date Created: 20130809 Date Completed: 20140519 Latest Revision: 20240610
- Publication Date:
20240610
- Accession Number:
PMC3973132
- Accession Number:
10.1126/scitranslmed.3006200
- Accession Number:
23926200
No Comments.