{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:51:05Z","timestamp":1791946265488,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,10,22]],"date-time":"2009-10-22T00:00:00Z","timestamp":1256169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Cancer Control R&D Program","award":["0820080"],"award-info":[{"award-number":["0820080"]}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Nuclear factor erythroid\u2010related factor 2<\/jats:italic> (<jats:italic>NRF2<\/jats:italic>) encodes a transcription factor that induces expression of cytoprotective proteins upon oxidative stress and oncogenic <jats:italic>NRF2<\/jats:italic> mutations have been found in lung and head\/neck cancers that inactivate KEAP1\u2010mediated degradation of NRF2. The aim of this study was to catalogue <jats:italic>NRF2<\/jats:italic> mutations in other human cancers. For this, we analysed 1145 cancer tissues from carcinomas from oesophagus, skin, uterine cervix, lung, larynx, breast, colon, stomach, liver, prostate, urinary bladder, ovary, uterine cervix, and kidney, and meningiomas, multiple myelomas, and acute leukaemias by single\u2010strand conformation polymorphism (SSCP) assay. We detected <jats:italic>NRF2<\/jats:italic> mutations in oesophagus (8\/70; 11.4%), skin (1\/17; 6.3%), lung (10\/125; 8.0%), and larynx (3\/23; 13.0%) cancers. Of note, all of the 22 mutations except one were found in squamous cell carcinomas (SCCs) (95.5%). The mutations were observed within or near DLG and ETGE motifs that are important in NRF2 and KEAP1 interaction. All of the oesophageal SCCs and skin SCCs with the <jats:italic>NRF2<\/jats:italic> mutations showed increased NRF2 expression in the nuclei. However, none of the SCCs from oesophagus and skin harboured <jats:italic>KEAP1<\/jats:italic> mutation. Our study demonstrated here that <jats:italic>NRF2<\/jats:italic> mutation occurs not only in lung and head\/neck cancers, but also in oesophageal and skin cancers. Our data suggest that the <jats:italic>NRF2<\/jats:italic> mutation plays a role in the development of SCC and is a feature of SCC. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2653","type":"journal-article","created":{"date-parts":[[2009,10,22]],"date-time":"2009-10-22T04:48:51Z","timestamp":1256186931000},"page":"446-451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":322,"title":["Oncogenic <i>NRF2<\/i> mutations in squamous cell carcinomas of oesophagus and skin"],"prefix":"10.1002","volume":"220","author":[{"given":"Yoo Ri","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Eun","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Sung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Ran","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Wook","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Youn","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Seok","family":"Eom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam Jin","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sug Hyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.981"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.12.4914-4923.2005"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.21.16023"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2001.00469.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100103200"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/03602530600971974"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.16.7130-7139.2004"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.1.221-229.2006"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.24.10941-10953.2004"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.21.9926"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2008.09.003"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1906"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.01.013"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030420"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806268105"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.8.2887-2900.2006"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601119200"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202769"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2029"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1248"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2007.39.4.139"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11698"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5742(00)00019-3"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30037"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.1.110304.100103"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji055"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800623"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.06.004"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2653","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2653","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2653","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:53:51Z","timestamp":1761047631000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,4]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,3]]}},"alternative-id":["10.1002\/path.2653"],"URL":"https:\/\/doi.org\/10.1002\/path.2653","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12,4]]},"assertion":[{"value":"2009-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}