{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:04:35Z","timestamp":1791245075387,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T00:00:00Z","timestamp":1418169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"crossref","award":["04-38"],"award-info":[{"award-number":["04-38"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:p>\n                    Aristolochic acid (AA) is a potent dietary cytotoxin and carcinogen, and an established etiological agent underlying severe human nephropathies and associated upper urinary tract urothelial cancers, collectively designated aristolochic acid nephropathy (AAN). Its genome\u2010wide mutational signature, marked by predominant A:T\u2009&gt;\u2009T:A transversions occurring in the 5\u2032\u2010CpApG\u20103\u2032 trinucleotide context and enriched on the nontranscribed gene strand, has been identified in human upper urinary tract urothelial carcinomas from East Asian patients and in experimental systems. Here we report a whole\u2010exome sequencing screen performed on DNA from formalin\u2010fixed, paraffin\u2010embedded renal cell carcinomas (RCC) arising in chronic renal disease patients from a Balkan endemic nephropathy (EN) region. In the EN regions, the disease results from the consumption of bread made from wheat contaminated by seeds of\n                    <jats:italic>Aristolochia clematitis,<\/jats:italic>\n                    an AA\u2010containing plant. In five of eight (62.5%) tested RCC tumor specimens, we observed the characteristic global mutational signature consistent with the mutagenic effects of AA. This signature was absent in the control RCC samples obtained from patients from a nonendemic, metropolitan region. By identifying a new tumor type associated with the AA\u2010driven genome\u2010wide mutagenic process in the context of renal disease, our results suggest new epidemiological and public health implications for the RCC incidence worldwide, particularly for the high\u2010risk regions with unregulated use of AA\u2010containing traditional herbal medicines.\n                  <\/jats:p>","DOI":"10.1002\/ijc.29338","type":"journal-article","created":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T00:14:16Z","timestamp":1416269656000},"page":"2967-2972","source":"Crossref","is-referenced-by-count":47,"title":["Renal cell carcinomas of chronic kidney disease patients harbor the mutational signature of carcinogenic aristolochic acid"],"prefix":"10.1002","volume":"136","author":[{"given":"Bojan","family":"Jelakovi\u0107","sequence":"first","affiliation":[{"name":"Department for Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center School of Medicine, University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Castells","sequence":"additional","affiliation":[{"name":"Molecular Mechanisms and Biomarkers Group International Agency for Research on Cancer Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Tomi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology Dr Josip Ben\u010devi\u0107 General Hospital Slavonski Brod Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Ardin","sequence":"additional","affiliation":[{"name":"Molecular Mechanisms and Biomarkers Group International Agency for Research on Cancer Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Karanovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center School of Medicine, University of Zagreb Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Zavadil","sequence":"additional","affiliation":[{"name":"Molecular Mechanisms and Biomarkers Group International Agency for Research on Cancer Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.129"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-6-201303190-00006"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21756"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701248104"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.371"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26077"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119920109"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2013.02.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006086"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050568"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00731.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1681\/ASN.V132431","article-title":"Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt\u2010depleted rats","volume":"13","author":"Debelle FD","year":"2002","journal-title":"J Am Soc Nephrol: JASN"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2391"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2295"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/9.2.297"},{"key":"e_1_2_7_18_1","first-page":"1203","article-title":"Comparison of occurrence of upper urinary tract carcinomas in the region with endemic villages and non\u2010endemic nephropathy region in Croatia","volume":"32","author":"Belicza M","year":"2008","journal-title":"Coll Antropol"},{"key":"e_1_2_7_19_1","first-page":"116","article-title":"Endemic nephropathy: the case for chronic poisoning by aristolochia","volume":"46","author":"Hranjec T","year":"2005","journal-title":"Croat Med J"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.154492.113"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-367"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep04482"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3729"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm541"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e4000"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.29338","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.29338","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T10:23:04Z","timestamp":1695982984000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.29338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,10]]},"references-count":25,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,6,15]]}},"alternative-id":["10.1002\/ijc.29338"],"URL":"https:\/\/doi.org\/10.1002\/ijc.29338","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,10]]}}}