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TP53 mutation signature supports involvement of aristolochic acid in the aetiology of endemic nephropathy‐associated tumours
Author(s) -
Nedelko Tatiana,
Arlt Volker M.,
Phillips David H.,
Hollstein Monica
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24006
Subject(s) - aristolochic acid , aristolochia , mutagen , mutation , biology , genetics , gene , concordance , cancer research , dna , botany
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.