{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:39:08Z","timestamp":1760297948590},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,7]]},"abstract":"Introduction<\/jats:title>Activating mutations of the BRAF<\/jats:italic> oncogene are frequently detected in papillary thyroid carcinoma (PTC) and have been associated with a worse prognosis. The amino acid substitution V600E accounts for 90% of all oncogenic BRAF<\/jats:italic> mutations and is typically detected in classic PTCs, whereas other less frequent BRAF<\/jats:italic> mutations seem to be associated with other PTC histotypes.<\/jats:p><\/jats:sec>Case<\/jats:title>Screening for activating BRAF<\/jats:italic> mutations in a series of 83 PTCs identified the most common V600E mutation in 39 cases (histologically, 38 classic PTCs and 1 sclerosing variant PTC) and a complex in-frame mutation involving amino acids V600\u2013S605 in a stage III multicentric follicular variant PTC, occurring in a 50-year-old female patient, who was affected by hypothyroidism in autoimmune thyroiditis and had a family history of PTC and autoimmune thyroiditis. Since the identified BRAF<\/jats:italic> mutation was novel in the literature, bioinformatic modeling was performed to predict its impact on BRAF activity. Although the mutation resulted in loss of a phosphorylation site in the activation loop of BRAF, it was predicted to increase BRAF kinase activity by mimicking an activating phosphorylation.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>This study, which reports a new BRAF<\/jats:italic> mutation, highlights the usefulness of bioinformatic modeling in the prediction of functional effects of new mutations and indicates that mutation-specific screening tests might miss some rare BRAF<\/jats:italic> mutations. These facts should be taken into consideration in the molecular diagnosis of thyroid cancer and in the design of therapeutic protocols based on inhibitors of the BRAF pathway.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-08-0239","type":"journal-article","created":{"date-parts":[[2008,4,22]],"date-time":"2008-04-22T00:15:17Z","timestamp":1208823317000},"page":"77-80","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":18,"title":["Characterization of a novel complex BRAF mutation in a follicular variant papillary thyroid carcinoma."],"prefix":"10.1093","volume":"159","author":[{"given":"Luisa","family":"Barzon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Masi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella Merante","family":"Boschin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Lavezzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monia","family":"Pacenti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Casal Ide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Toniato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Toppo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Pal\u00f9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rosa","family":"Pelizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"issue":"6892","key":"1_17120961","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/nature00766","volume":"417","author":"Davies","year":"2002","journal-title":"Nature; 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