{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:38:52Z","timestamp":1791895132644,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Brown tumors are giant cell\u2010rich lesions that result from abnormal bone metabolism in hyperparathyroidism, one of the most common endocrine disorders worldwide. Brown tumors occasionally affect the jaws and, despite well\u2010known clinical and microscopic features, their molecular pathogenesis remains unclear. We investigated the presence of pathogenic activating mutations in <jats:italic>TRPV4<\/jats:italic>, <jats:italic>FGFR1<\/jats:italic>, and <jats:italic>KRAS<\/jats:italic> in a cohort of brown tumors since these have recently been reported in giant\u2010cell lesions of the jaws and non\u2010ossifying fibromas of the bones (<jats:italic>FGFR1<\/jats:italic> and <jats:italic>KRAS<\/jats:italic>), which are histologic mimics of brown tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We target sequenced 13 brown tumors of the jaws associated with primary or secondary hyperparathyroidism. As mutations in these genes are known to activate the MAPK\/ERK signaling pathway, we also assessed the immunostaining of the phosphorylated form of ERK1\/2 (pERK1\/2) in these lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>KRAS<\/jats:italic> pathogenic mutations were detected in seven cases (p.G12V n\u00a0=\u00a04, p.G12D n\u00a0=\u00a01, p.G13D n\u00a0=\u00a01, p.A146T n\u00a0=\u00a01). <jats:italic>KRAS<\/jats:italic> variants of unknown significance (VUS), p.A134T and p.E37K, were also detected. All samples showed wild\u2010type sequences for <jats:italic>FGFR<\/jats:italic>1 and <jats:italic>TRPV4<\/jats:italic> genes. The activation of the MAPK\/ERK signaling pathway was demonstrated by pERK1\/2 immunohistochemical positivity of the brown tumors\u00b4 mononuclear cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Mutations in <jats:italic>KRAS<\/jats:italic> and activation of the MAPK\/ERK signaling pathway were detected in brown tumors of hyperparathyroidism of the jaws, expanding the spectrum of giant cell lesions whose molecular pathogenesis involve RAS signaling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.13048","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T21:41:18Z","timestamp":1591220478000},"page":"796-802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<i>KRAS<\/i> mutations in brown tumor of the jaws in hyperparathyroidism"],"prefix":"10.1111","volume":"49","author":[{"given":"Let\u00edcia Martins","family":"Guimar\u00e3es","sequence":"first","affiliation":[{"name":"Department of Oral Surgery and Pathology School of Dentistry Universidade Federal de Minas Gerais (UFMG) Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora Pereira","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery and Pathology School of Dentistry Universidade Federal de Minas Gerais (UFMG) Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tha\u00eds dos Santos Fontes","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery and Pathology School of Dentistry Universidade Federal de Minas Gerais (UFMG) Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Augusto Benevenuto","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis and Pathology School of Dentistry Universidade Federal do Rio de Janeiro (UFRJ) Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rio Jos\u00e9","family":"Roma\u00f1ach","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis and Pathology School of Dentistry Universidade Federal do Rio de Janeiro (UFRJ) Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falio C\u00e9sar Tanos","family":"de Lacerda","sequence":"additional","affiliation":[{"name":"Stomatology Service of Hospital Odilon Behrens Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lder Ant\u00f4nio Rebelo","family":"Pontes","sequence":"additional","affiliation":[{"name":"Service of Oral Pathology Hospital Universit\u00e1rio Jo\u00e3o de Barros Barreto Universidade Federal do Par\u00e1 (UFPA) Bel\u00e9m Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Queen Alexandra Hospital Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siavash","family":"Rahimi","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences University of Portsmouth Portsmouth UK"},{"name":"Frontier Pathology\u2010Royal Sussex County Hospital Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rom\u00e1n","family":"Carlos","sequence":"additional","affiliation":[{"name":"Centro Clinico de Cabeza y Cuello Guatemala City Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalberto","family":"Mosqueda\u2010Taylor","sequence":"additional","affiliation":[{"name":"Health Care Department Universidad Aut\u00f3noma Metropolitana Xochimilco 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