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oai:repisalud.isciii.es:20.500.12105/260682025-12-18T12:56:54Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author Burnichon, Nelly author Cascon Soriano, Alberto author Schiavi, Francesca author Morales, Nicole Paes author Comino-Méndez, Iñaki author Abermil, Nasséra author Inglada-Pérez, Lucía author de Cubas, Aguirre A author Amar, Laurence author Barontini, Marta author de Quirós, Sandra Bernaldo author Bertherat, Jérôme author Bignon, Yves-Jean author Blok, Marinus J author Bobisse, Sara author Borrego, Salud author Castellano, Maurizio author Chanson, Philippe author Chiara, María-Dolores author Corssmit, Eleonora P M author Giacchè, Mara author de Krijger, Ronald R author Ercolino, Tonino author Girerd, Xavier author Gómez-García, Encarna B author Gómez-Graña, Alvaro author Guilhem, Isabelle author Hes, Frederik J author Honrado, Emiliano author Korpershoek, Esther author Lenders, Jacques W M author Letón, Rocío author Mensenkamp, Arjen R author Merlo, Anna author Mori, Luigi author Murat, Arnaud author Pierre, Peggy author Plouin, Pierre-François author Prodanov, Tamara author Quesada-Charneco, Miguel author Qin, Nan author Rapizzi, Elena author Raymond, Victoria author Reisch, Nicole author Roncador, Giovanna author Ruiz-Ferrer, Macarena author Schillo, Frank author Stegmann, Alexander P A author Suarez, Carlos author Taschin, Elisa author Timmers, Henri J L M author Tops, Carli M J author Urioste, Miguel author Beuschlein, Felix author Pacak, Karel author Mannelli, Massimo author Dahia, Patricia L M author Opocher, Giuseppe author Eisenhofer, Graeme author Gimenez-Roqueplo, Anne-Paule author Robledo, Mercedes funder Instituto de Salud Carlos III funder fundacion MUTUA MADRILEÑA funder JUNTA DE ANDALUCIA funder Agence Nationale de la Recherche (ANR) funder United States Department of Health & Human Services National Institutes of Health (NIH) - USA 2025-01-20T12:32:29Z 2025-01-20T12:32:29Z 2012-05-15 Clin Cancer Res . 2012 May 15;18(10):2828-37 CLINICAL CANCER RESEARCH 22452945 https://hdl.handle.net/20.500.12105/26068 Pheochromocytomas (PCC) and paragangliomas (PGL) are genetically heterogeneous neural crest-derived neoplasms. Recently we identified germline mutations in a new tumor suppressor susceptibility gene, MAX (MYC-associated factor X), which predisposes carriers to PCC. How MAX mutations contribute to PCC/PGL and associated phenotypes remain unclear. This study aimed to examine the prevalence and associated phenotypic features of germline and somatic MAX mutations in PCC/PGL.We sequenced MAX in 1,694 patients with PCC or PGL (without mutations in other major susceptibility genes) from 17 independent referral centers. We screened for large deletions/duplications in 1,535 patients using a multiplex PCR-based method. Somatic mutations were searched for in tumors from an additional 245 patients. The frequency and type of MAX mutation was assessed overall and by clinical characteristics.Sixteen MAX pathogenic mutations were identified in 23 index patients. All had adrenal tumors, including 13 bilateral or multiple PCCs within the same gland (P < 0.001), 15.8% developed additional tumors at thoracoabdominal sites, and 37% had familial antecedents. Age at diagnosis was lower (P = 0.001) in MAX mutation carriers compared with nonmutated cases. Two patients (10.5%) developed metastatic disease. A mutation affecting MAX was found in five tumors, four of them confirmed as somatic (1.65%). MAX tumors were characterized by substantial increases in normetanephrine, associated with normal or minor increases in metanephrine.Germline mutations in MAX are responsible for 1.12% of PCC/PGL in patients without evidence of other known mutations and should be considered in the genetic work-up of these patients. eng MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. research article 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 URL https://repisalud.isciii.es/bitstreams/a248ddcc-b6b7-48db-8c0e-74d7dcc2a3d4/download File MD5 2b126d800dff52699121411ea2d52b44 555144 application/pdf maxmutations-2012.pdf URL https://repisalud.isciii.es/bitstreams/7222f79a-7262-4221-8d14-19c5b392d78e/download File MD5 24d37414477cf4d12d679569956ba918 40912 application/vnd.openxmlformats-officedocument.wordprocessingml.document Carátula repisalud.docx