Integrated genomic characterization of adrenocortical carcinoma

Guillaume Assié; Eric Letouzé; Martin Fassnacht; Anne Jouinot; Windy Luscap; Olivia Barreau; Hanin Omeiri; Stéphanie Rodriguez; Karine Perlemoine; Fernande René-Corail; Nabila Elarouci; Silviu Sbiera; Matthias Kroiss; Bruno Allolio; Jens Waldmann; Marcus Quinkler; Massimo Mannelli; Franco Mantero; Thomas Papathomas; Ronald De Krijger; Antoine Tabarin; Véronique Kerlan; Eric Baudin; Frédérique Tissier; Bertrand Dousset; Lionel Groussin; Laurence Amar; Eric Clauser; Xavier Bertagna; Bruno Ragazzon; Felix Beuschlein; Rossella Libé; Aurélien De Reyniès; Jérôme Bertherat

doi:10.1038/ng.2953

Integrated genomic characterization of adrenocortical carcinoma

Guillaume Assié, Eric Letouzé, Martin Fassnacht, Anne Jouinot, Windy Luscap, Olivia Barreau, Hanin Omeiri, Stéphanie Rodriguez, Karine Perlemoine, Fernande René-Corail, Nabila Elarouci, Silviu Sbiera, Matthias Kroiss, Bruno Allolio, Jens Waldmann, Marcus Quinkler, Massimo Mannelli, Franco Mantero, Thomas Papathomas, Ronald De KrijgerAntoine Tabarin, Véronique Kerlan, Eric Baudin, Frédérique Tissier, Bertrand Dousset, Lionel Groussin, Laurence Amar, Eric Clauser, Xavier Bertagna, Bruno Ragazzon, Felix Beuschlein, Rossella Libé, Aurélien De Reyniès, Jérôme Bertherat

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland. Despite overall poor prognosis, ACC outcome is heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the Î 2-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.

Originele taal-2	Engels
Pagina's (van-tot)	607-612
Aantal pagina's	6
Tijdschrift	Nature Genetics
Volume	46
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1038/ng.2953
Status	Gepubliceerd - jun. 2014
Extern gepubliceerd	Ja

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10.1038/ng.2953

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Assié, G., Letouzé, E., Fassnacht, M., Jouinot, A., Luscap, W., Barreau, O., Omeiri, H., Rodriguez, S., Perlemoine, K., René-Corail, F., Elarouci, N., Sbiera, S., Kroiss, M., Allolio, B., Waldmann, J., Quinkler, M., Mannelli, M., Mantero, F., Papathomas, T., ... Bertherat, J. (2014). Integrated genomic characterization of adrenocortical carcinoma. Nature Genetics, 46(6), 607-612. https://doi.org/10.1038/ng.2953

@article{4b8dbcdeb6ea428eab296a5ab7333533,

title = "Integrated genomic characterization of adrenocortical carcinoma",

abstract = "Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland. Despite overall poor prognosis, ACC outcome is heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the {\^I} 2-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.",

author = "Guillaume Assi{\'e} and Eric Letouz{\'e} and Martin Fassnacht and Anne Jouinot and Windy Luscap and Olivia Barreau and Hanin Omeiri and St{\'e}phanie Rodriguez and Karine Perlemoine and Fernande Ren{\'e}-Corail and Nabila Elarouci and Silviu Sbiera and Matthias Kroiss and Bruno Allolio and Jens Waldmann and Marcus Quinkler and Massimo Mannelli and Franco Mantero and Thomas Papathomas and {De Krijger}, Ronald and Antoine Tabarin and V{\'e}ronique Kerlan and Eric Baudin and Fr{\'e}d{\'e}rique Tissier and Bertrand Dousset and Lionel Groussin and Laurence Amar and Eric Clauser and Xavier Bertagna and Bruno Ragazzon and Felix Beuschlein and Rossella Lib{\'e} and {De Reyni{\`e}s}, Aur{\'e}lien and J{\'e}r{\^o}me Bertherat",

note = "Funding Information: We thank F. Letourneur, R. Pelletier and S. Jacques from the Genomic platform of the Cochin Institute and P. Nietscke from the Paris Descartes University Bioinformatics platform for their technical support, J. M{\'e}tral and J. Godet from the Ligue Nationale Contre le Cancer for organization of the Cartes d{\textquoteright}Identit{\'e} des Tumeurs (CIT) program, P.F. Plouin for organization of the COMETE network, the tumor bank of Cochin Hospital (B. Terris and M. Sibony) for help in sample collection, the Oncogenetic Department of Cochin Hospital (V. Duchossoy), A. Steel for management of the ENSAT database, the members of our laboratories and the COMETE and ENSAT networks for support and discussions, and all the staffs of the clinical and pathology departments who were involved in patient care. This study is part of the CIT Program from La Ligue Nationale Contre le Cancer. It was supported by funding from the Programme Hospitalier de Recherche Clinique to the COMETE network (grant AOM95201), the Seventh Framework Programme (FP7/2007-2013) under grant agreement 259735, Institut National du Cancer Recherche Translationelle 2009-RT-02, the Institut National du Cancer (to the Rare Adrenal Cancer Network COMETE), INSERM (G.A. receives a Contrat d{\textquoteright}Interface) and the Conny-Maeva Charitable Foundation (to the laboratory of J.B.).",

year = "2014",

month = jun,

doi = "10.1038/ng.2953",

language = "English",

volume = "46",

pages = "607--612",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

Assié, G, Letouzé, E, Fassnacht, M, Jouinot, A, Luscap, W, Barreau, O, Omeiri, H, Rodriguez, S, Perlemoine, K, René-Corail, F, Elarouci, N, Sbiera, S, Kroiss, M, Allolio, B, Waldmann, J, Quinkler, M, Mannelli, M, Mantero, F, Papathomas, T, De Krijger, R, Tabarin, A, Kerlan, V, Baudin, E, Tissier, F, Dousset, B, Groussin, L, Amar, L, Clauser, E, Bertagna, X, Ragazzon, B, Beuschlein, F, Libé, R, De Reyniès, A & Bertherat, J 2014, 'Integrated genomic characterization of adrenocortical carcinoma', Nature Genetics, vol. 46, nr. 6, blz. 607-612. https://doi.org/10.1038/ng.2953

TY - JOUR

T1 - Integrated genomic characterization of adrenocortical carcinoma

AU - Assié, Guillaume

AU - Letouzé, Eric

AU - Fassnacht, Martin

AU - Jouinot, Anne

AU - Luscap, Windy

AU - Barreau, Olivia

AU - Omeiri, Hanin

AU - Rodriguez, Stéphanie

AU - Perlemoine, Karine

AU - René-Corail, Fernande

AU - Elarouci, Nabila

AU - Sbiera, Silviu

AU - Kroiss, Matthias

AU - Allolio, Bruno

AU - Waldmann, Jens

AU - Quinkler, Marcus

AU - Mannelli, Massimo

AU - Mantero, Franco

AU - Papathomas, Thomas

AU - De Krijger, Ronald

AU - Tabarin, Antoine

AU - Kerlan, Véronique

AU - Baudin, Eric

AU - Tissier, Frédérique

AU - Dousset, Bertrand

AU - Groussin, Lionel

AU - Amar, Laurence

AU - Clauser, Eric

AU - Bertagna, Xavier

AU - Ragazzon, Bruno

AU - Beuschlein, Felix

AU - Libé, Rossella

AU - De Reyniès, Aurélien

AU - Bertherat, Jérôme

N1 - Funding Information: We thank F. Letourneur, R. Pelletier and S. Jacques from the Genomic platform of the Cochin Institute and P. Nietscke from the Paris Descartes University Bioinformatics platform for their technical support, J. Métral and J. Godet from the Ligue Nationale Contre le Cancer for organization of the Cartes d’Identité des Tumeurs (CIT) program, P.F. Plouin for organization of the COMETE network, the tumor bank of Cochin Hospital (B. Terris and M. Sibony) for help in sample collection, the Oncogenetic Department of Cochin Hospital (V. Duchossoy), A. Steel for management of the ENSAT database, the members of our laboratories and the COMETE and ENSAT networks for support and discussions, and all the staffs of the clinical and pathology departments who were involved in patient care. This study is part of the CIT Program from La Ligue Nationale Contre le Cancer. It was supported by funding from the Programme Hospitalier de Recherche Clinique to the COMETE network (grant AOM95201), the Seventh Framework Programme (FP7/2007-2013) under grant agreement 259735, Institut National du Cancer Recherche Translationelle 2009-RT-02, the Institut National du Cancer (to the Rare Adrenal Cancer Network COMETE), INSERM (G.A. receives a Contrat d’Interface) and the Conny-Maeva Charitable Foundation (to the laboratory of J.B.).

PY - 2014/6

Y1 - 2014/6

N2 - Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland. Despite overall poor prognosis, ACC outcome is heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the Î 2-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.

AB - Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland. Despite overall poor prognosis, ACC outcome is heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the Î 2-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.

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U2 - 10.1038/ng.2953

DO - 10.1038/ng.2953

M3 - Article

C2 - 24747642

AN - SCOPUS:84901648115

SN - 1061-4036

VL - 46

SP - 607

EP - 612

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Integrated genomic characterization of adrenocortical carcinoma

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