{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:24:26Z","timestamp":1765959866215,"version":"3.40.4"},"reference-count":0,"publisher":"S. Karger AG","issue":"3-4","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytogenet Genome Res"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>Pheochromocytomas (PCC) and sympathetic paragangliomas (PGL) are rare neuroendocrine tumors, which derive from chromaffin cells occurring in the adrenal medulla and extra-adrenal sympathetic paraganglia. PCC and PGL are often benign, catecholamine-producing tumors, responsible for a myriad of symptoms that may be potentially hazardous to the patient. In contrast, nonsecreting parasympathetic PGL, derived from chief cells, develop mainly in the head and neck region. Although PCC\/PGL are more commonly sporadic tumors, germline mutations are present in up to 40% of the patients, ranking these tumors among those with the highest degree of heritability. PCC\/PGL are associated with a variety of hereditary syndromes, comprising genetic alterations in &lt;i&gt;RET&lt;\/i&gt;, &lt;i&gt;NF1&lt;\/i&gt;, &lt;i&gt;VHL&lt;\/i&gt;, and &lt;i&gt;SDHx&lt;\/i&gt; genes, the last 2 being involved in regulating the hypoxia pathway. Additional hypoxia pathway-related genes have been recently associated with PCC\/PGL development, namely &lt;i&gt;EGLN1&lt;\/i&gt; and &lt;i&gt;EPAS1&lt;\/i&gt;. Thus, dysregulation of the hypoxia pathway seems to play a major role in PCC\/PGL development, in particular through the stabilization of hypoxia-inducible factors and the appearance of a pseudohypoxia signature. This article is focused on reviewing the tumorigenic mechanisms resultant from &lt;i&gt;VHL&lt;\/i&gt;, &lt;i&gt;SDHx&lt;\/i&gt;, &lt;i&gt;EGLN1&lt;\/i&gt;, and &lt;i&gt;EPAS1&lt;\/i&gt; mutations, as well as the associated tumors, namely PCC\/PGL, and extra manifestations such as polycythemia. In the light of the recent discoveries, hypoxia pathway molecules appear as key players in PCC\/PGL development.<\/jats:p>","DOI":"10.1159\/000457479","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T22:06:56Z","timestamp":1487887616000},"page":"227-241","source":"Crossref","is-referenced-by-count":18,"title":["Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas"],"prefix":"10.1159","volume":"150","author":[{"given":"Diana","family":"Amorim-Pires","sequence":"first","affiliation":[]},{"given":"Joana","family":"Peixoto","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Lima","sequence":"additional","affiliation":[]}],"member":"127","published-online":{"date-parts":[[2017,2,24]]},"container-title":["Cytogenetic and Genome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/457479","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/457479","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/457479","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:27:44Z","timestamp":1745429264000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000457479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":0,"journal-issue":{"issue":"3-4","published-online":{"date-parts":[[2017,3,28]]},"published-print":{"date-parts":[[2017,3,28]]}},"URL":"https:\/\/doi.org\/10.1159\/000457479","archive":["Portico"],"relation":{},"ISSN":["1424-8581","1424-859X"],"issn-type":[{"type":"print","value":"1424-8581"},{"type":"electronic","value":"1424-859X"}],"subject":[],"published":{"date-parts":[[2016]]}}}