TY - JOUR
T1 - Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma
AU - Comino-Méndez, Iñaki
AU - Gracia-Aznárez, Francisco J.
AU - Schiavi, Francesca
AU - Landa, Iñigo
AU - Leandro-García, Luis J.
AU - Letón, Rocío
AU - Honrado, Emiliano
AU - Ramos-Medina, Rocío
AU - Caronia, Daniela
AU - Pita, Guillermo
AU - Gómez-Graña, Álvaro
AU - De Cubas, Aguirre A.
AU - Inglada-Pérez, Lucía
AU - Maliszewska, Agnieszka
AU - Taschin, Elisa
AU - Bobisse, Sara
AU - Pica, Giuseppe
AU - Loli, Paola
AU - Hernández-Lavado, Rafael
AU - Díaz, José A.
AU - Gómez-Morales, Mercedes
AU - González-Neira, Anna
AU - Roncador, Giovanna
AU - Rodríguez-Antona, Cristina
AU - Benítez, Javier
AU - Mannelli, Massimo
AU - Opocher, Giuseppe
AU - Robledo, Mercedes
AU - Cascón, Alberto
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
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U2 - 10.1038/ng.861
DO - 10.1038/ng.861
M3 - Article
C2 - 21685915
AN - SCOPUS:79959752614
VL - 43
SP - 663
EP - 667
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 7
ER -