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The approach they use is immunodetection of proteins that have been modified by a non\u2010enzymatic reaction of thiol groups in proteins with fumarate, which is termed succination. Validation included the use of mice with targeted inactivation of fumarate hydratase in the kidney, extensive studies of normal human tissues and examination of over 1000 specimens from human cancers not associated with <jats:italic>FH<\/jats:italic> mutations. Detection of protein succination is likely to provide a sensitive and specific method for pathologists to identify the small proportion of papillary renal cell carcinomas that are associated with germline mutations in the <jats:italic>FH<\/jats:italic> gene. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2950","type":"journal-article","created":{"date-parts":[[2011,6,7]],"date-time":"2011-06-07T10:48:12Z","timestamp":1307443692000},"page":"1-3","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Seeing the smoking gun: a sensitive and specific method to visualize loss of the tumour suppressor, fumarate hydratase, in human tissues"],"prefix":"10.1002","volume":"225","author":[{"given":"Patrick H.","family":"Maxwell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,7,25]]},"reference":[{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2932"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng849"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61757-9"},{"key":"e_1_2_3_5_2","first-page":"537","article-title":"Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors","volume":"10","author":"Delahunt B","year":"1997","journal-title":"Mod Pathol"},{"key":"e_1_2_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi227"},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.06.017"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00483-09"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq305"},{"key":"e_1_2_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.02.005"},{"key":"e_1_2_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2009.08.018"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.03.015"},{"key":"e_1_2_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703551200"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2950","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2950","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2950","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:14:05Z","timestamp":1761041645000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7,25]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1002\/path.2950"],"URL":"https:\/\/doi.org\/10.1002\/path.2950","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"type":"print","value":"0022-3417"},{"type":"electronic","value":"1096-9896"}],"subject":[],"published":{"date-parts":[[2011,7,25]]},"assertion":[{"value":"2011-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-06-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-07-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}