{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T09:00:07Z","timestamp":1766998807540,"version":"3.48.0"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objective: To comprehensively characterize the genetic landscape of medullary thyroid carcinoma (MTC) in a Romanian cohort. Methods: Germline and somatic RET testing were performed in 164 MTC patients (105 sporadic, 59 hereditary) consecutively enrolled at a single tertiary center (2021\u20132024) using genomic DNA or DNA extracted from fresh surgical or paraffin-embedded pathology specimens. Results: Hereditary MTC (hMTC) accounted for 59\/164 (35.9%) cases. Among hMTC, 58\/59 (98.3%) had MEN2 (72.4% classic, 5.2% with cutaneous lichen amyloidosis, 5.2% with Hirschsprung disease, and 17.2% with familial medullary thyroid carcinoma), and 1\/59 (1.7%) had MEN3. Codon 634 mutations were the most prevalent (33\/59, 55.9%). Extracellular cysteine-rich domain mutations were significantly more prevalent in syndromic cases (p = 0.006), while non-cysteine mutations were predominant in apparently sporadic cases (p = 0.006). In advanced MTC (stage III\/IV or metastatic), the somatic M918T mutation was the most common (15\/20, 75% cases). Conclusions: Germline RET screening is mandatory for all MTC cases. Somatic testing is critical in advanced disease, where M918T prevails in 75% of cases and guides tyrosine kinase inhibitor therapy. Codon 634 is the most frequent mutation in Romanian MTC, highlighting regional variation warranting population-adjusted screening and earlier prophylactic thyroidectomy.<\/jats:p>","DOI":"10.3390\/cancers18010093","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T08:47:27Z","timestamp":1766998047000},"page":"93","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Landscape of Phenotype-Genotype Correlations in Romanian Patients with Medullary Thyroid Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"given":"Laura-Semonia","family":"Stanescu","sequence":"first","affiliation":[{"name":"Department of Endocrinology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 0505474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia-Maria","family":"Lider-Burciulescu","sequence":"additional","affiliation":[{"name":"Department of Physiology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 0505474 Bucharest, Romania"},{"name":"\u201dAna Aslan\u201d, National Institute of Geriatrics and Gerontology, 011241 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei","family":"Muresan","sequence":"additional","affiliation":[{"name":"Department of Research, \u201cCI Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4886-2174","authenticated-orcid":false,"given":"Sorina Violeta","family":"Schipor","sequence":"additional","affiliation":[{"name":"Department of Research, \u201cCI Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Braha","sequence":"additional","affiliation":[{"name":"Department of Research, \u201cCI Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1754-5619","authenticated-orcid":false,"given":"Monica Livia","family":"Gheorghiu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 0505474 Bucharest, Romania"},{"name":"Department of Research, \u201cCI Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-8125","authenticated-orcid":false,"given":"Corin","family":"Badiu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 0505474 Bucharest, Romania"},{"name":"Department of Research, \u201cCI Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1089\/thy.2014.0335","article-title":"Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma","volume":"25","author":"Wells","year":"2015","journal-title":"Thyroid"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/ajcp\/95.3.300","article-title":"Medullary thyroid cancer. 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