TP53 mutation signature supports involvement of aristolochic acid in the aetiology of endemic nephropathy-associated tumours
Article first published online: 19 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 124, Issue 4, pages 987–990, 15 February 2009
How to Cite
Nedelko, T., Arlt, V. M., Phillips, D. H. and Hollstein, M. (2009), TP53 mutation signature supports involvement of aristolochic acid in the aetiology of endemic nephropathy-associated tumours. Int. J. Cancer, 124: 987–990. doi: 10.1002/ijc.24006
- Issue published online: 11 DEC 2008
- Article first published online: 19 SEP 2008
- Accepted manuscript online: 19 SEP 2008 12:00AM EST
- Manuscript Accepted: 25 AUG 2008
- Manuscript Received: 11 JUL 2008
- Association for International Cancer Research (UK)
- cancer aetiology;
The proposal has been put forward that the primary cause of Balkan endemic nephropathy (BEN) is exposure to food crops contaminated with seeds of Aristolochia spp, which contain high levels of aristolochic acids (AA). Recently, tumour DNA samples from patients with BEN were found to harbour principally A to T mutations in the TP53 tumour suppressor gene (Grollman et al., Proc Natl Acad Sci USA 2007;104:12129–34). Using a novel mutation assay in which we can induce and select mutations in human TP53 sequences in vitro by exposure of cultured cells to a mutagen, we found that A to T mutations were elicited by aristolochic acid at sites in TP53 rarely mutated in human cancers in general, but which were observed in the BEN patients. This concordance of specific mutations in patient tumours and aristolochic acid I-exposed cultures supports the argument that AA has a direct role in the aetiology of BEN-associated cancer. © 2008 Wiley-Liss, Inc.