{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T15:10:36Z","timestamp":1777648236053,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,11,17]],"date-time":"2009-11-17T00:00:00Z","timestamp":1258416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:p>Park SW, Chung NG, Hur SY, Kim HS, Yoo NJ, Lee SH. Mutational analysis of hypoxia\u2010related genes <jats:italic>HIF1\u03b1<\/jats:italic> and <jats:italic>CUL2<\/jats:italic> in common human cancers. APMIS 2009; 117: 880\u20135.<\/jats:p><jats:p>Hypoxia is a general feature of solid cancer tissues. Hypoxia upregulates hypoxia\u2010inducible factor 1\u03b1 (HIF1\u03b1) that transactivates downstream genes and contributes to cancer pathogenesis. HIF1\u03b1 is upregulated not only by hypoxia but also by genetic alterations in HIF1\u03b1\u2010related genes, including <jats:italic>VHL<\/jats:italic>. Cullin 2 (CUL2) interacts with the trimeric VHL\u2010elongin B\u2010elongin C complex and plays an essential role in the ubiquitinated degradation of HIF1\u03b1. The aim of this study was to explore whether <jats:italic>HIF1\u03b1<\/jats:italic> and <jats:italic>CUL2<\/jats:italic> genes are somatically mutated, and contribute to HIF1\u03b1 activation in common human cancers. For this, we have analyzed the coding region of oxygen\u2010dependent degradation domain of <jats:italic>HIF1\u03b1<\/jats:italic> in 47 colon, 47 gastric, 47 breast, 47 lung, and 47 hepatocellular carcinomas, and 47 acute leukemias by a single\u2010strand conformation polymorphism assay. In addition, we analyzed mononucleotide repeat sequences (A8) in <jats:italic>CUL2<\/jats:italic> in 55 colorectal and 45 gastric carcinomas with microsatellite instability (MSI). We found one <jats:italic>HIF1\u03b1<\/jats:italic> mutation (p.Ala593Pro) in the hepatocellular carcinomas (1\/47; 2.1%), but none in other cancers. We found two <jats:italic>CUL2<\/jats:italic> frameshift mutations in colon cancers (p.Asn292MetfsX20), which were exclusively detected in high MSI cancers (4.9%; 2\/41). Our data indicate that somatic mutation of <jats:italic>HIF1\u03b1<\/jats:italic> is rare in common cancers, and somatic mutation of <jats:italic>CUL2<\/jats:italic> occurs in a fraction of colorectal cancers (colorectal cancers with high MSI). The data suggest that neither <jats:italic>HIF1\u03b1<\/jats:italic> nor <jats:italic>CUL2<\/jats:italic> mutation may play a central role in <jats:italic>HIF1\u03b1<\/jats:italic> activation in gastric, colorectal, breast, lung and hepatocellular carcinomas, and acute leukemias.<\/jats:p>","DOI":"10.1111\/j.1600-0463.2009.02550.x","type":"journal-article","created":{"date-parts":[[2009,11,17]],"date-time":"2009-11-17T22:02:58Z","timestamp":1258495378000},"page":"880-885","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mutational analysis of hypoxia\u2010related genes <i>HIF1\u03b1<\/i> and <i>CUL2<\/i> in common human cancers"],"prefix":"10.1111","volume":"117","author":[{"given":"SANG WOOK","family":"PARK","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"NAK 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