{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:06:31Z","timestamp":1753862791700,"version":"3.41.2"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hypoxia\u2010inducible factor\u20102\u03b1 (HIF\u20102\u03b1) modulates the hypoxic response pathway in tumors; however, mutations in pathways (including SDHA, SDHB, SDHC, SDHD, FH, and VHL genes) that are suspected to activate HIF\u20102\u03b1 are poorly understood, with limited understanding of the prevalence and clinical prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective observational study used a de\u2010identified nationwide (US\u2010based) clinico\u2010genomic database (CGDB) across 15 available tumor types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 9467 adult patients with advanced\/metastatic solid tumors included in the analysis, any mutation at the above\u2010mentioned six genes was observed in 1.8% (95% CI: 1.5\u20132.1) of patients. The mutation prevalence ranged from 0.05% of SDHD to 0.93% of VHL. When further stratified by tumor type, the prevalence of gene mutation in each tumor type was well below 1%, except for VHL with 44% in renal cell carcinomas (RCC). Excluding RCC, the prevalence of any HIF\u20102\u03b1 gene mutations in the study population was 0.9% (95% CI: 0.8\u20131.2). The median overall survival (OS) from 1 and 2\u2009L therapy among patients with any HIF\u20102\u03b1 gene mutation was 14.5 (95% CI: 11.5\u201324.2) and 9.3 (95% CI: 6.0\u201318.1)\u2009months, respectively, compared with 13.4 (95% CI: 12.9\u201313.9) and 9.8 (95% CI: 9.3\u201310.4) months among patients without HIF\u20102\u03b1 gene mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and Conclusions<\/jats:title><jats:p>The prevalence of HIF\u20102\u03b1 related gene mutations was generally low (&lt;1%) across the 15 solid tumor types, except for VHL in RCC. No significant association between HIF\u20102\u03b1 gene mutation status and OS was identified among patients evaluated in this study.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7358","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T11:34:11Z","timestamp":1718192051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence and prognosis of hypoxia\u2010inducible factor\u20102\u03b1 (<scp>HIF<\/scp>\u20102\u03b1) pathway gene mutations across advanced solid tumors"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0135-4500","authenticated-orcid":false,"given":"Wenjun","family":"Zhong","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiemin","family":"Ma","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cai","family":"Chen","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. J.","family":"Dettman","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Razvan","family":"Cristescu","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girish S.","family":"Naik","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Jin","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  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