{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:32:06Z","timestamp":1774312326893,"version":"3.50.1"},"reference-count":118,"publisher":"Bioscientifica","issue":"5","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Medullary thyroid carcinoma (MTC) is a rare malignancy originating from the calcitonin-secreting parafollicular thyroid C cells. Approximately 75% of cases are sporadic. Rearranged during transfection (<jats:italic>RET<\/jats:italic>) proto-oncogene plays a crucial role in MTC development. Besides<jats:italic>RET<\/jats:italic>, other oncogenes commonly involved in the pathogenesis of human cancers have also been investigated in MTC. The family of human<jats:italic>RAS<\/jats:italic>genes includes the highly homologous<jats:italic>HRAS<\/jats:italic>,<jats:italic>KRAS<\/jats:italic>, and<jats:italic>NRAS<\/jats:italic>genes that encode three distinct proteins. Activating mutations in specific hotspots of the<jats:italic>RAS<\/jats:italic>genes are found in about 30% of all human cancers. In thyroid neoplasias,<jats:italic>RAS<\/jats:italic>gene point mutations, mainly in<jats:italic>NRAS<\/jats:italic>, are detected in benign and malignant tumors arising from the follicular epithelium. However, recent reports have also described<jats:italic>RAS<\/jats:italic>mutations in MTC, namely in<jats:italic>HRAS<\/jats:italic>and<jats:italic>KRAS<\/jats:italic>. Overall, the prevalence of<jats:italic>RAS<\/jats:italic>mutations in sporadic MTC varies between 0\u201343.3%, occurring usually in tumors with WT<jats:italic>RET<\/jats:italic>and rarely in those harboring a<jats:italic>RET<\/jats:italic>mutation, suggesting that activation of these proto-oncogenes represents alternative genetic events in sporadic MTC tumorigenesis. Thus, the assessment of<jats:italic>RAS<\/jats:italic>mutation status can be useful to define therapeutic strategies in<jats:italic>RET<\/jats:italic>WT MTC. MTC patients with<jats:italic>RAS<\/jats:italic>mutations have an intermediate risk for aggressive cancer, between those with<jats:italic>RET<\/jats:italic>mutations in exons 15 and 16, which are associated with the worst prognosis, and cases with other<jats:italic>RET<\/jats:italic>mutations, which have the most indolent course of the disease. Recent results from exome sequencing indicate that, besides mutations in<jats:italic>RET<\/jats:italic>,<jats:italic>HRAS<\/jats:italic>, and<jats:italic>KRAS<\/jats:italic>, no other recurrent driver mutations are present in MTC.<\/jats:p>","DOI":"10.1530\/erc-15-0070","type":"journal-article","created":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T03:19:40Z","timestamp":1439954380000},"page":"R235-R252","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":96,"title":["RAS proto-oncogene in medullary thyroid carcinoma"],"prefix":"10.1530","volume":"22","author":[{"given":"Margarida M","family":"Moura","sequence":"first","affiliation":[]},{"given":"Branca M","family":"Cavaco","sequence":"additional","affiliation":[]},{"given":"Valeriano","family":"Leite","sequence":"additional","affiliation":[]}],"member":"416","reference":[{"key":"2015081820185408000_22.5.R235.1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0242"},{"key":"2015081820185408000_22.5.R235.2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2703"},{"key":"2015081820185408000_22.5.R235.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2012.03.002"},{"key":"2015081820185408000_22.5.R235.4","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2008.0403"},{"key":"2015081820185408000_22.5.R235.5","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23999"},{"key":"2015081820185408000_22.5.R235.6","doi-asserted-by":"crossref","unstructured":"Bockhorn M Frilling A Kalinin V Schr\u00f6der S Broelsch CE 2000 Absence of H- and K-ras oncogene mutations in sporadic medullary thyroid carcinoma. 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