Skip to Main content Skip to Navigation
Journal articles

MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma.

Nelly Burnichon 1, 2, 3 Alberto Cascón Francesca Schiavi Nicole Paes Morales Iñaki Comino-Méndez Nasséra Abermil Lucía Inglada-Pérez Aguirre A de Cubas Laurence Amar 1, 3, 4 Marta Barontini 5 Sandra Bernaldo de Quirós Jérôme Bertherat 6 Yves-Jean Bignon 7, 8 Marinus J Blok 9, 10 Sara Bobisse Salud Borrego 11, 12 Maurizio Castellano Philippe Chanson 13 María-Dolores Chiara Eleonora P M Corssmit Mara Giacchè Ronald R de Krijger 14 Tonino Ercolino Xavier Girerd Encarna B Gómez-García Alvaro Gómez-Graña Isabelle Guilhem 15 Frederik J Hes Emiliano Honrado Esther Korpershoek Jacques W M Lenders Rocío Letón Arjen R Mensenkamp Anna Merlo Luigi Mori Arnaud Murat Peggy Pierre 16 Pierre-François Plouin 1, 3, 4 Tamara Prodanov Miguel Quesada-Charneco Nan Qin 17 Elena Rapizzi Victoria Raymond Nicole Reisch Giovanna Roncador 18 Macarena Ruiz-Ferrer Frank Schillo Alexander P A Stegmann Carlos Suarez Elisa Taschin Henri J L M Timmers Carli M J Tops Miguel Urioste 19 Felix Beuschlein Karel Pacak Massimo Mannelli Patricia L M Dahia Giuseppe Opocher 20 Graeme Eisenhofer 21 Anne-Paule Gimenez-Roqueplo 1, 2, 3 Mercedes Robledo 22, *
Abstract : PURPOSE: 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. Design: 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. RESULTS: 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. CONCLUSIONS: 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.
Document type :
Journal articles
Complete list of metadata
Contributor : Camille Meyer <>
Submitted on : Friday, July 25, 2014 - 11:14:18 AM
Last modification on : Wednesday, October 14, 2020 - 3:50:41 AM

Links full text



Nelly Burnichon, Alberto Cascón, Francesca Schiavi, Nicole Paes Morales, Iñaki Comino-Méndez, et al.. MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma.. Clinical Cancer Research, American Association for Cancer Research, 2012, 18 (10), pp.2828-37. ⟨10.1158/1078-0432.CCR-12-0160⟩. ⟨hal-01048691⟩



Record views