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. Díaz; Mercedes Gómez-Morales; Anna González-Neira; Giovanna Roncador; Cristina Rodríguez-Antona; Javier Benítez; Massimo Mannelli; Giuseppe Opocher; Mercedes Robledo; Alberto Cascón

doi:10.1038/ng.861

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

Istituto Oncologico Veneto

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English
Pages (from-to)	663-667
Number of pages	5
Journal	Nature Genetics
Volume	43
Issue number	7
DOIs	https://doi.org/10.1038/ng.861
Publication status	Published - Jul 2011

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.861

Fingerprint Dive into the research topics of 'Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma'. Together they form a unique fingerprint.

Cite this

Comino-Méndez, I., Gracia-Aznárez, F. J., Schiavi, F., Landa, I., Leandro-García, L. J., Letón, R., Honrado, E., Ramos-Medina, R., Caronia, D., Pita, G., Gómez-Graña, Á., De Cubas, A. A., Inglada-Pérez, L., Maliszewska, A., Taschin, E., Bobisse, S., Pica, G., Loli, P., Hernández-Lavado, R., ... Cascón, A. (2011). Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nature Genetics, 43(7), 663-667. https://doi.org/10.1038/ng.861

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

In: Nature Genetics, Vol. 43, No. 7, 07.2011, p. 663-667.

Research output: Contribution to journal › Article › peer-review

Comino-Méndez, I, Gracia-Aznárez, FJ, Schiavi, F, Landa, I, Leandro-García, LJ, Letón, R, Honrado, E, Ramos-Medina, R, Caronia, D, Pita, G, Gómez-Graña, Á, De Cubas, AA, Inglada-Pérez, L, Maliszewska, A, Taschin, E, Bobisse, S, Pica, G, Loli, P, Hernández-Lavado, R, Díaz, JA, Gómez-Morales, M, González-Neira, A, Roncador, G, Rodríguez-Antona, C, Benítez, J, Mannelli, M, Opocher, G, Robledo, M & Cascón, A 2011, 'Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma', Nature Genetics, vol. 43, no. 7, pp. 663-667. https://doi.org/10.1038/ng.861

Comino-Méndez, Iñaki ; Gracia-Aznárez, Francisco J. ; Schiavi, Francesca ; Landa, Iñigo ; Leandro-García, Luis J. ; Letón, Rocío ; Honrado, Emiliano ; Ramos-Medina, Rocío ; Caronia, Daniela ; Pita, Guillermo ; Gómez-Graña, Álvaro ; De Cubas, Aguirre A. ; Inglada-Pérez, Lucía ; Maliszewska, Agnieszka ; Taschin, Elisa ; Bobisse, Sara ; Pica, Giuseppe ; Loli, Paola ; Hernández-Lavado, Rafael ; Díaz, José A. ; Gómez-Morales, Mercedes ; González-Neira, Anna ; Roncador, Giovanna ; Rodríguez-Antona, Cristina ; Benítez, Javier ; Mannelli, Massimo ; Opocher, Giuseppe ; Robledo, Mercedes ; Cascón, Alberto. / Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. In: Nature Genetics. 2011 ; Vol. 43, No. 7. pp. 663-667.

@article{7da2403f367c49d0bea6b7b7bc53f959,

title = "Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma",

abstract = "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.",

author = "I{\~n}aki Comino-M{\'e}ndez and Gracia-Azn{\'a}rez, {Francisco J.} and Francesca Schiavi and I{\~n}igo Landa and Leandro-Garc{\'i}a, {Luis J.} and Roc{\'i}o Let{\'o}n and Emiliano Honrado and Roc{\'i}o Ramos-Medina and Daniela Caronia and Guillermo Pita and {\'A}lvaro G{\'o}mez-Gra{\~n}a and {De Cubas}, {Aguirre A.} and Luc{\'i}a Inglada-P{\'e}rez and Agnieszka Maliszewska and Elisa Taschin and Sara Bobisse and Giuseppe Pica and Paola Loli and Rafael Hern{\'a}ndez-Lavado and D{\'i}az, {Jos{\'e} A.} and Mercedes G{\'o}mez-Morales and Anna Gonz{\'a}lez-Neira and Giovanna Roncador and Cristina Rodr{\'i}guez-Antona and Javier Ben{\'i}tez and Massimo Mannelli and Giuseppe Opocher and Mercedes Robledo and Alberto Casc{\'o}n",

year = "2011",

month = jul,

doi = "10.1038/ng.861",

language = "English",

volume = "43",

pages = "663--667",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "7",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=79959752614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959752614&partnerID=8YFLogxK

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 -