{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:18:57Z","timestamp":1791029937520,"version":"4.1.0"},"reference-count":32,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The tumorigenesis of sporadic endocrine tumors is still not fully understood. Activating point mutations of the serine\/threonine kinase gene BRAF located on 7q34 are found in a wide range of malignancies, with the highest frequency (66%) occurring in malignant melanomas. Melanomas are tumors of neural-crest-derived cells as are medullary thyroid carcinomas, pheochromocytomas and paragangliomas. BRAF has not been examined in endocrine tumors of the diffuse neuroendocrine system or of neural-crest-derived cells.<\/jats:p>\n                  <jats:p>We examined 130 endocrine tumors of the pancreas, parathyroid gland, adrenal medulla, paraganglia, lung and gastrointestinal tract as well as follicular and c-cell-derived thyroid tumors. We found a high rate of V559E mutations in papillary thyroid carcinomas (47%), one V599E mutation in a well-differentiated gastric endocrine carcinoma (malignant carcinoid), but no activating BRAF mutations in all other endocrine tumors examined. These results point towards different pathways in tumorigenesis of endocrine tumors of various localizations and only rare involvement of the MAP kinase (MAPK) pathway in a subset of malignant neuroendocrine tumors.<\/jats:p>","DOI":"10.1677\/erc.1.00841","type":"journal-article","created":{"date-parts":[[2005,1,21]],"date-time":"2005-01-21T16:19:42Z","timestamp":1106324382000},"page":"855-860","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":30,"title":["<i>BRAF<\/i>\n                    and endocrine tumors: mutations are frequent in papillary thyroid carcinomas, rare in endocrine tumors of the gastrointestinal tract and not detected in other endocrine tumors"],"prefix":"10.1530","volume":"11","author":[{"given":"A","family":"Perren","sequence":"first","affiliation":[{"name":"Institute for Clinical Pathology, Department of Pathologie, University Hospital Zu\u0308rich, Schmelzbergstr. 12, CH-8091, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Schmid","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pathology, Department of Pathologie, University Hospital Zu\u0308rich, Schmelzbergstr. 12, CH-8091, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Locher","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pathology, Department of Pathologie, University Hospital Zu\u0308rich, Schmelzbergstr. 12, CH-8091, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Saremaslani","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pathology, Department of Pathologie, University Hospital Zu\u0308rich, Schmelzbergstr. 12, CH-8091, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Bonvin","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pathology, Department of Pathologie, University Hospital Zu\u0308rich, Schmelzbergstr. 12, CH-8091, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P U","family":"Heitz","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pathology, Department of Pathologie, University Hospital Zu\u0308rich, Schmelzbergstr. 12, CH-8091, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Komminoth","sequence":"additional","affiliation":[{"name":"1Institut for Clinical Pathology, Kantonsspital Baden, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2026070905543886000_AGARWAL-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Agarwal\n            SK\n          , Schrock E, Kester MB, Burns AL, Heffess CS, Ried T & Marx SJ 1998 Comparative genomic hybridization analysis of human parathyroid tumors. Cancer Genetics and Cytogenetics10630\u201336.","DOI":"10.1016\/S0165-4608(98)00049-1"},{"key":"2026070905543886000_COHEN-ETAL-2003","doi-asserted-by":"crossref","unstructured":"Cohen\n            Y\n          , Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW & Sidransky D 2003 BRAF mutation in papillary thyroid carcinoma. Journal of the National Cancer Institute95625\u2013627.","DOI":"10.1093\/jnci\/95.8.625"},{"key":"2026070905543886000_DAHIA-ETAL-1997","unstructured":"Dahia\n            PL\n          , Marsh DJ, Zheng Z, Zedenius J, Komminoth P, Frisk T, Wallin G, Parsons R, Longy M, Larsson C et al.1997 Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. Cancer Research574710\u20134713."},{"key":"2026070905543886000_DAVIES-ETAL-2002","unstructured":"Davies\n            H\n          , Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W et al.2002 Mutations of the BRAF gene in human cancer. Nature417949\u2013954."},{"key":"2026070905543886000_DUPIN-AND-LE-DOUARIN-2003","doi-asserted-by":"crossref","unstructured":"Dupin\n            E\n           & Le Douarin NM 2003 Development of melanocyte precursors from the vertebrate neural crest. Oncogene223016\u20133023.","DOI":"10.1038\/sj.onc.1206460"},{"key":"2026070905543886000_EDSTROM-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Edstrom\n            E\n          , Mahlamaki E, Nord B, Kjellman M, Karhu R, Hoog A, Goncharov N, Teh BT, Backdahl M & Larsson C 2000 Comparative genomic hybridization reveals frequent losses of chromosomes 1p and 3q in pheochromocytomas and abdominal paragangliomas, suggesting a common genetic etiology. American Journal of Pathology156651\u2013659.","DOI":"10.1016\/S0002-9440(10)64769-4"},{"key":"2026070905543886000_FUKUSHIMA-ETAL-2003","doi-asserted-by":"crossref","unstructured":"Fukushima\n            T\n          , Suzuki S, Mashiko M, Ohtake T, Endo Y, Takebayashi Y, Sekikawa K, Hagiwara K & Takenoshita S 2003 BRAF mutations in papillary carcinomas of the thyroid. Oncogene226455\u20136457.","DOI":"10.1038\/sj.onc.1206739"},{"key":"2026070905543886000_GIMM-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Gimm\n            O\n          , Perren A, Weng LP, Marsh DJ, Yeh JJ, Ziebold U, Gil E, Hinze R, Delbridge L, Lees JA et al.2000 Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors. American Journal of Pathology1561693\u20131700.","DOI":"10.1016\/S0002-9440(10)65040-7"},{"key":"2026070905543886000_KIMURA-ETAL-2003","unstructured":"Kimura\n            ET\n          , Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE & Fagin JA 2003 High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET\/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Research631454\u20131457."},{"key":"2026070905543886000_KOMMINOTH-ETAL-1994","unstructured":"Komminoth\n            P\n          , Kunz E, Hiort O, Schroder S, Matias-Guiu X, Christiansen G, Roth J & Heitz PU 1994 Detection of RET protooncogene point mutations in paraffin-embedded pheochromocytoma specimens by nonradioactive single-strand conformation polymorphism analysis and direct sequencing. American Journal of Pathology145922\u2013929."},{"key":"2026070905543886000_KOMMINOTH-ETAL-1995","unstructured":"Komminoth\n            P\n          , Kunz EK, Matias-Guiu X, Hiort O, Christiansen G, Colomer A, Roth J & Heitz PU 1995 Analysis of RET protooncogene point mutations distinguishes heritable from nonheritable medullary thyroid carcinomas. Cancer76479\u2013489."},{"key":"2026070905543886000_LIEBMANN-2001","doi-asserted-by":"crossref","unstructured":"Liebmann\n            C\n          \n          2001 Regulation of MAP kinase activity by peptide receptor signalling pathway: paradigms of multiplicity. Cellular Signalling13777\u2013785.","DOI":"10.1016\/S0898-6568(01)00192-9"},{"key":"2026070905543886000_NAMBA-ETAL-2003","doi-asserted-by":"crossref","unstructured":"Namba\n            H\n          , Nakashima M, Hayashi T, Hayashida N, Maeda S, Rogounovitch TI, Ohtsuru A, Saenko VA, Kanematsu T & Yamashita S 2003 Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. Journal of Clinical Endocrinology and Metabolism884393\u20134397.","DOI":"10.1210\/jc.2003-030305"},{"key":"2026070905543886000_NIKIFOROVA-ETAL-2003","doi-asserted-by":"crossref","unstructured":"Nikiforova\n            MN\n          , Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, Zhu Z, Giannini R, Salvatore G, Fusco A et al.2003 BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. Journal of Clinical Endocrinology and Metabolism885399\u20135404.","DOI":"10.1210\/jc.2003-030838"},{"key":"2026070905543886000_PASINI-ETAL-1996","unstructured":"Pasini\n            A\n          , Michiels FM, Chappuis-Flament S, Geneste O, Rossel M, Fournier L, Feunteun J, Lenoir G, Schuffenecker I & Billaud M 1996 Neural crest and multiple endocrinopathies. Comptes rendus des seances de la Societe de biologie et de ses filiales190557\u2013567."},{"key":"2026070905543886000_PERISSEL-ETAL-2002","unstructured":"Perissel\n            B\n          , Bernheim A, Couturier J, Fouilhoux G, Vago P & Oncologique GF 2002 De la cytogenetique a la cytogenomique des tumeurs de la thyroide. Bulletin du Cancer89588\u2013592."},{"key":"2026070905543886000_PERREN-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Perren\n            A\n          , Roth J, Muletta-Feurer S, Saremaslani P, Speel EJ, Heitz PU & Komminoth P 1998 Clonal analysis of sporadic pancreatic endocrine tumours. Journal of Pathology186363\u2013371.","DOI":"10.1002\/(SICI)1096-9896(199812)186:4<363::AID-PATH197>3.0.CO;2-W"},{"key":"2026070905543886000_PERREN-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Perren\n            A\n          , Komminoth P, Saremaslani P, Matter C, Feurer S, Lees JA, Heitz PU & Eng C 2000 Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. American Journal of Pathology1571097\u20131103.","DOI":"10.1016\/S0002-9440(10)64624-X"},{"key":"2026070905543886000_PUXEDDU-ETAL-2004","doi-asserted-by":"crossref","unstructured":"Puxeddu\n            E\n          , Moretti S, Elisei R, Romei C, Pascucci R, Martinelli M, Marino C, Avenia N, Rossi ED, Fadda G et al.2004 BRAF(V599E) mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas. Journal of Clinical Endocrinology and Metabolism892414\u20132420.","DOI":"10.1210\/jc.2003-031425"},{"key":"2026070905543886000_RAJAGOPALAN-ETAL-2002","doi-asserted-by":"crossref","unstructured":"Rajagopalan\n            H\n          , Bardelli A, Lengauer C, Kinzler KW, Vogelstein B & Velculescu VE 2002 Tumorigenesis: RAF\/RAS oncogenes and mismatch-repair status. Nature418934.","DOI":"10.1038\/418934a"},{"key":"2026070905543886000_ROQUE-ETAL-1999","unstructured":"Roque\n            L\n          , Serpa A, Clode A, Castedo S & Soares J 1999 Significance of trisomy 7 and 12 in thyroid lesions with follicular differentiation: a cytogenetic and in situ hybridization study. Laboratory Investigations79369\u2013378."},{"key":"2026070905543886000_SINGH-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Singh\n            B\n          , Lim D, Cigudosa JC, Ghossein R, Shaha AR, Poluri A, Wreesmann VB, Tuttle M, Shah JP & Rao PH 2000 Screening for genetic aberrations in papillary thyroid cancer by using comparative genomic hybridization. Surgery128888\u2013893 (discussion, 893\u2013894).","DOI":"10.1067\/msy.2000.110847"},{"key":"2026070905543886000_SOARES-ETAL-2003","doi-asserted-by":"crossref","unstructured":"Soares\n            P\n          , Trovisco V, Rocha AS, Lima J, Castro P, Preto A, Maximo V, Botelho T, Seruca R & Sobrinho-Simoes M 2003 BRAF mutations and RET\/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene224578\u20134580.","DOI":"10.1038\/sj.onc.1206706"},{"key":"2026070905543886000_SOARES-ETAL-2004","doi-asserted-by":"crossref","unstructured":"Soares\n            P\n          , Trovisco V, Rocha AS, Feijao T, Rebocho AP, Fonseca E, Vieira de Castro I, Cameselle-Teijeiro J, Cardoso-Oliveira M & Sobrinho-Simoes M 2004 BRAF mutations typical of papillary thyroid carcinoma are more frequently detected in undifferentiated than in insular and insular-like poorly differentiated carcinomas. Virchows Archiv444572\u2013576.","DOI":"10.1007\/s00428-004-1018-0"},{"key":"2026070905543886000_SPEEL-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Speel\n            EJ\n          , Richter J, Moch H, Egenter C, Saremaslani P, Rutimann K, Zhao J, Barghorn A, Roth J, Heitz PU et al.1999 Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization. American Journal of Pathology1551787\u20131794.","DOI":"10.1016\/S0002-9440(10)65495-8"},{"key":"2026070905543886000_SPEEL-ETAL-2001","unstructured":"Speel\n            EJ\n          , Scheidweiler AF, Zhao J, Matter C, Saremaslani P, Roth J, Heitz PU & Komminoth P 2001 Genetic evidence for early divergence of small functioning and nonfunctioning endocrine pancreatic tumors: gain of 9Q34 is an early event in insulinomas. Cancer Research615186\u20135192."},{"key":"2026070905543886000_STUMPF-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Stumpf\n            E\n          , Aalto Y, Hoog A, Kjellman M, Otonkoski T, Knuutila S & Andersson LC 2000 Chromosomal alterations in human pancreatic endocrine tumors. Genes, Chromosomes and Cancer2983\u201387.","DOI":"10.1002\/1098-2264(2000)9999:9999<::AID-GCC1011>3.0.CO;2-Z"},{"key":"2026070905543886000_TROVISCO-ETAL-2004","doi-asserted-by":"crossref","unstructured":"Trovisco\n            V\n          , Vieira de Castro I, Soares P, Maximo V, Silva P, Magalhaes J, Abrosimov A, Guiu XM & Sobrinho-Simoes M 2004 BRAF mutations are associated with some histological types of papillary thyroid carcinoma. Journal of Pathology202247\u2013251.","DOI":"10.1002\/path.1511"},{"key":"2026070905543886000_VAN-DER-HARST-ETAL-1998","doi-asserted-by":"crossref","unstructured":"van der Harst\n            E\n          , de Krijger RR, Bruining HA, Lamberts SW, Bonjer HJ, Dinjes WN, Proye C, Koper JW, Bosman FT, Roth J et al.1998 Prognostic value of RET proto-oncogene point mutations in malignant and benign, sporadic phaeochromocytomas. International Journal of Cancer79537\u2013540.","DOI":"10.1002\/(SICI)1097-0215(19981023)79:5<537::AID-IJC16>3.0.CO;2-Z"},{"key":"2026070905543886000_XING-ETAL-2004","doi-asserted-by":"crossref","unstructured":"Xing\n            M\n          , Vasko V, Tallini G, Larin A, Wu G, Udelsman R, Ringel MD, Ladenson PW & Sidransky D 2004 BRAF T1796A transversion mutation in various thyroid neoplasms. Journal of Clinical Endocrinology and Metabolism891365\u20131368.","DOI":"10.1210\/jc.2003-031488"},{"key":"2026070905543886000_XU-ETAL-2003","unstructured":"Xu\n            X\n          , Quiros RM, Gattuso P, Ain KB & Prinz RA 2003 High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Research634561\u20134567."},{"key":"2026070905543886000_ZHAO-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Zhao\n            J\n          , de Krijger RR, Meier D, Speel EJ, Saremaslani P, Muletta-Feurer S, Matter C, Roth J, Heitz PU & Komminoth P 2000 Genomic alterations in well-differentiated gastrointestinal and bronchial neuroendocrine tumors (carcinoids): marked differences indicating diversity in molecular pathogenesis. American Journal of Pathology1571431\u20131438.","DOI":"10.1016\/S0002-9440(10)64780-3"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/11\/4\/0110855.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article-pdf\/11\/4\/855\/149528\/0110855.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article-pdf\/11\/4\/855\/149528\/0110855.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T09:54:51Z","timestamp":1783590891000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article\/11\/4\/855\/26631\/BRAF-and-endocrine-tumors-mutations-are-frequent"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,1]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,12,1]]}},"URL":"https:\/\/doi.org\/10.1677\/erc.1.00841","relation":{},"ISSN":["1479-6821","1351-0088"],"issn-type":[{"value":"1479-6821","type":"electronic"},{"value":"1351-0088","type":"print"}],"subject":[],"published":{"date-parts":[[2004,12,1]]}}}