{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:51:20Z","timestamp":1775278280824,"version":"3.50.1"},"reference-count":0,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,9]]},"abstract":"Our main objective was to search for mutations in candidate genes and for paired box gene 8\u2013peroxisome proliferator-activated receptor gamma (PAX8\u2013PPAR\u03b3<\/jats:italic>) rearrangement in a well-differentiated angioinvasive follicular thyroid carcinoma (FTC) causing hyperthyroidism. DNA and RNA were extracted from the patient's thyroid tumor, as well as \u2018normal\u2019 thyroid tissue, and from peripheral blood lymphocytes (PBLs) of the patient, her daughter, and two siblings. Nuclear isolation was extracted from the patient's tumor, \u2019normal\u2019 thyroid tissue, PBLs, and uterine leiomyoma tissue. TSH receptor (TSHR<\/jats:italic>), RAS<\/jats:italic>, and BRAF<\/jats:italic> genes were sequenced. We searched for PAX8<\/jats:italic>\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic> in thyroid, PBL, and uterine leiomyoma samples from the patient and family members. Proliferative effects of detected mutants on non-transformed human thyrocytes cultures. An activating TSHR mutation, M453T, was detected in the tumor. PAX8<\/jats:italic> (exons 1<\/jats:italic>\u2013<\/jats:italic>8<\/jats:italic>+<\/jats:italic>10<\/jats:italic>)\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic> was found in all tested patient's tissues. A second rearrangement, PAX8<\/jats:italic> (exons 1<\/jats:italic>\u2013<\/jats:italic>8<\/jats:italic>)\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic>, was detected in the patient's normal thyroid tissue. Under deprived medium condition, co-transfection of PAX8<\/jats:italic>\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic> and TSHR<\/jats:italic>\u2013<\/jats:italic>M453T<\/jats:italic> dramatically increased the number of thyrocytes, an effect that it was not observed with TSHR wild-type (WT); under complete medium conditions, co-transfection of PAX8<\/jats:italic>\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic> with either TSHR<\/jats:italic>\u2013<\/jats:italic>M453T<\/jats:italic> or TSHR<\/jats:italic>\u2013<\/jats:italic>WT<\/jats:italic> inhibited cell proliferation. We report a patient with hyperthyroidism due to a FTC bearing an activating TSHR mutation and PAX8<\/jats:italic>\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic> rearrangements. PAX8<\/jats:italic>\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic> was present as a mosaicism affecting tissues from endodermal and mesodermal origin. PAX8<\/jats:italic>\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic> and TSHR<\/jats:italic>\u2013<\/jats:italic>M453T<\/jats:italic> inhibited or promoted thyrocyte proliferation depending on medium conditions. The activating TSHR<\/jats:italic> mutation could promote in vivo<\/jats:italic> FTC development in PAX8<\/jats:italic>\u2013<\/jats:italic>PPAR<\/jats:italic>\u03b3<\/jats:italic>-positive thyrocytes under poor blood supply with deprivation of growth factors but restraint the tumor growth when growth factors are supplied.<\/jats:p>","DOI":"10.1677\/erc-09-0069","type":"journal-article","created":{"date-parts":[[2010,4,29]],"date-time":"2010-04-29T01:01:12Z","timestamp":1272502872000},"page":"599-610","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":15,"title":["Identification of a paired box gene 8\u2013peroxisome proliferator-activated receptor gamma (PAX8\u2013PPAR\u03b3) rearrangement mosaicism in a patient with an autonomous functioning follicular thyroid carcinoma bearing an activating mutation in the TSH receptor"],"prefix":"10.1530","volume":"17","author":[{"given":"J","family":"Lado-Abeal","sequence":"first","affiliation":[]},{"given":"R","family":"Celestino","sequence":"additional","affiliation":[]},{"given":"S B","family":"Bravo","sequence":"additional","affiliation":[]},{"given":"M E R","family":"Garcia-Rendueles","sequence":"additional","affiliation":[]},{"given":"J","family":"de la Calzada","sequence":"additional","affiliation":[]},{"given":"I","family":"Castro","sequence":"additional","affiliation":[]},{"given":"P","family":"Castro","sequence":"additional","affiliation":[]},{"given":"C","family":"Espadinha","sequence":"additional","affiliation":[]},{"given":"F","family":"Palos","sequence":"additional","affiliation":[]},{"given":"P","family":"Soares","sequence":"additional","affiliation":[]},{"given":"C V","family":"Alvarez","sequence":"additional","affiliation":[]},{"given":"M","family":"Sobrinho-Sim\u00f5es","sequence":"additional","affiliation":[]},{"given":"J","family":"Cameselle-Teijeiro","sequence":"additional","affiliation":[]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/17\/3\/599.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/17\/3\/599.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T21:31:19Z","timestamp":1676583079000},"score":1,"resource":{"primary":{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/17\/3\/599.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1677\/erc-09-0069","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9]]}}}