{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:43:26Z","timestamp":1791863006670,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,5,22]],"date-time":"2007-05-22T00:00:00Z","timestamp":1179792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2007,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Germline mutations in nuclear genes encoding mitochondrial enzymes fumarate hydratase (FH) and succinate dehydrogenase (subunits SDHB\/C\/D) have been implicated in the development of tumor syndromes referred to as hereditary leiomyomatosis and renal cell cancer (HLRCC) and hereditary paragangliomatosis (HPGL), respectively. FH and SDH are operating in the tricarboxylic acid cycle (the TCA cycle, the Krebs cycle). In the FH and SDH deficient tumors, accumulation of the substrates, fumarate and succinate, has been shown to cause stabilization of hypoxia inducible factor 1\u03b1 (HIF1\u03b1). According to recent studies, HIF1\u03b1 could contribute to the hypoxia induced genomic instability seen in many cancers, through repression of mismatch repair (MMR) protein MSH2. In this study, in agreement with previous works, we found HIF1\u03b1 to be moderately or highly stabilized in 67% (16\/24) and 77% (48\/62) of HLRCC tumors and\n                    <jats:italic>SDHB\/C\/D<\/jats:italic>\n                    paragangliomas (PGL) and pheochromocytomas (PHEO), respectively. In addition, a set of 54 other familial and nonfamilial PGLs\/PHEOs were studied. Moderately or highly stabilized HIF1\u03b1 was present in 68% (26\/38) of the PGLs but in PHEOs (\n                    <jats:italic>n<\/jats:italic>\n                    = 16) no such pattern was observed. We then analyzed the suggested link between HIF1\u03b1 stabilization and MSH2 repression, in HLRCC and HPGL tumor material. No microsatellite instability (MSI) or lack of MSH2 expression was, however, observed. Thus we failed to provide\n                    <jats:italic>in vivo<\/jats:italic>\n                    evidence for the proposed link between HIF1\u03b1 stabilization and functional MMR deficiency, in TCAC deficient tumors. \u00a9 2007 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ijc.22819","type":"journal-article","created":{"date-parts":[[2007,5,26]],"date-time":"2007-05-26T20:32:15Z","timestamp":1180211535000},"page":"1386-1389","source":"Crossref","is-referenced-by-count":22,"title":["Increased HIF1\u03b1 in SDH and FH deficient tumors does not cause microsatellite instability"],"prefix":"10.1002","volume":"121","author":[{"given":"Heli J.","family":"Lehtonen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus J.","family":"M\u00e4kinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maija","family":"Kiuru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"Laiho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riitta","family":"Herva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne van","family":"Minderhout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pancras C.W.","family":"Hogendoorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cees","family":"Cornelisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Devilee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virpi","family":"Launonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri A.","family":"Aaltonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,7,23]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051633798"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng849"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5454.848"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.20.2347"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/381054"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.11.022"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi227"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1686"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.06.017"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-006-0133-6"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.02.015"},{"key":"e_1_2_6_13_2","first-page":"5830","article-title":"Overexpression 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