{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T18:40:23Z","timestamp":1722364823840},"reference-count":0,"publisher":"Wiley","issue":"5-6","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Analytical Cellular Pathology"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:p>Gliosarcomas are rare and poorly characterized malignant brain tumors that exhibit a biphasic tissue pattern with areas of gliomatous and sarcomatous differentiation. These tumors are histological variants of glioblastoma, displaying a similar genetic profile and dismal prognosis. Up\u2010regulation of PDGFR subfamily of tyrosine kinase members, PDGFR\u2010<jats:italic>\u03b1<\/jats:italic> and c\u2010Kit, and their intracellular effectors RAS\/RAF\/MAPK has a crucial role in the cancer development. In addition, signal transduction mediated by activating mutations of <jats:italic>c<\/jats:italic>\u2010Kit and <jats:italic>PDGFR<\/jats:italic> can be effectively blocked by specific tyrosine kinase inhibitors, such as Imatinib mesylate. The aim of this study was to characterize the molecular alterations of PDGFR signaling in gliosarcomas. Six cases were analyzed by immunohistochemistry for the expression of PDGFR\u2010<jats:italic>\u03b1<\/jats:italic>, c\u2010Kit and their ligands PDGF\u2010A and SCF, respectively. The cases were further evaluated for the presence of activating mutations of PDGFR\u2010<jats:italic>\u03b1<\/jats:italic> (exons 12 and 18) and c\u2010kit (exons 9, 11, 13, and 17), as well as <jats:italic>B-RAF<\/jats:italic> (exons 11 and 15). Expression of PDGF\u2010A was found in all cases and co\u2010expression of PDGFR\u2010<jats:italic>\u03b1<\/jats:italic> was observed in three cases. Four cases showed expression of SCF, and <jats:italic>c<\/jats:italic>\u2010Kit was observed only in one case that also expressed SCF. Generally, immunoreaction predominates in the glial component. The mutational analysis of PDGFR\u2010<jats:italic>\u03b1<\/jats:italic> showed the presence of an IVS17\u201050insT intronic insertion in two cases, one of them also with a 2472C &gt; T silent mutation; this silent mutation was also found in another case. Glioma cell line analysis of IVS17\u201050insT insertion showed no influence on PDGFR\u2010<jats:italic>\u03b1<\/jats:italic> gene splicing. No mutations were detected in c\u2010kit and <jats:italic>B-RAF<\/jats:italic> oncogenes. Our Results indicate that activating mutations of PDGFR\u2010<jats:italic>\u03b1<\/jats:italic>, <jats:italic>c<\/jats:italic>\u2010kit and <jats:italic>B-RAF<\/jats:italic> are absent in gliosarcomas. Nevertheless, the presence of a PDGFR\u2010a\/PDGFA and <jats:italic>c<\/jats:italic>\u2010Kit\/SCF autocrine\/paracrine stimulation loop in a proportion of cases, supports the potential role of specific tyrosine kinase inhibitors in the treatment of gliosarcomas.<\/jats:p>","DOI":"10.1155\/2005\/347863","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T16:31:19Z","timestamp":1611246679000},"page":"319-326","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Characterization of PDGFR\u2010<i>\u03b1<\/i>\/PDGF\u2010A and c\u2010KIT\/SCF in Gliosarcomas"],"prefix":"10.1155","volume":"27","author":[{"given":"Rui M.","family":"Reis","sequence":"first","affiliation":[]},{"given":"Albino","family":"Martins","sequence":"additional","affiliation":[]},{"given":"Susana A.","family":"Ribeiro","sequence":"additional","affiliation":[]},{"given":"Diana","family":"Basto","sequence":"additional","affiliation":[]},{"given":"Adhemar","family":"Longatto-Filho","sequence":"additional","affiliation":[]},{"given":"Fernando C.","family":"Schmitt","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 M.","family":"Lopes","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,1]]},"container-title":["Analytical Cellular Pathology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/acp\/2005\/347863.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2005\/347863","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T17:44:24Z","timestamp":1722361464000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2005\/347863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1]]},"references-count":0,"journal-issue":{"issue":"5-6","published-print":{"date-parts":[[2005,1]]}},"alternative-id":["10.1155\/2005\/347863"],"URL":"https:\/\/doi.org\/10.1155\/2005\/347863","archive":["Portico"],"relation":{},"ISSN":["2210-7177","2210-7185"],"issn-type":[{"type":"print","value":"2210-7177"},{"type":"electronic","value":"2210-7185"}],"subject":[],"published":{"date-parts":[[2005,1]]},"assertion":[{"value":"2005-01-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}