Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma

Iñaki Comino-Méndez, Francisco J. Gracia-Aznárez, Francesca Schiavi, Iñigo Landa, Luis J. Leandro-García, Rocío Letón, Emiliano Honrado, Rocío Ramos-Medina, Daniela Caronia, Guillermo Pita, Álvaro Gómez-Graña, Aguirre A. De Cubas, Lucía Inglada-Pérez, Agnieszka Maliszewska, Elisa Taschin, Sara Bobisse, Giuseppe Pica, Paola Loli, Rafael Hernández-Lavado, José A. DíazMercedes Gómez-Morales, Anna González-Neira, Giovanna Roncador, Cristina Rodríguez-Antona, Javier Benítez, Massimo Mannelli, Giuseppe Opocher, Mercedes Robledo, Alberto Cascón

Research output: Contribution to journalArticlepeer-review


Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.

Original languageEnglish
Pages (from-to)663-667
Number of pages5
JournalNature Genetics
Issue number7
Publication statusPublished - Jul 2011

ASJC Scopus subject areas

  • Genetics


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