Integrated genomic characterization of adrenocortical carcinoma.

Guillaume Assié 1, 2 Eric Letouzé 3 Martin Fassnacht 4, 5, 6 Anne Jouinot Windy Luscap Olivia Barreau 1, 2 Hanin Omeiri 7 Stéphanie Rodriguez 8 Karine Perlemoine 7 Fernande René-Corail 1 Nabila Elarouci 9 Silviu Sbiera 4, 6 Matthias Kroiss Bruno Allolio 5, 6 Jens Waldmann Marcus Quinkler Massimo Mannelli Franco Mantero Thomas Papathomas Ronald De Krijger 10, 11 Antoine Tabarin 12 Véronique Kerlan 13 Eric Baudin 14, 15 Frédérique Tissier 7 Bertrand Dousset Lionel Groussin Laurence Amar 16 Eric Clauser Xavier Bertagna 1, 17 Bruno Ragazzon Felix Beuschlein 4 Rossella Libé Aurélien De Reyniès 18 Jérôme Bertherat 7
1 UMR_S567 / UMR 8104 - Institut Cochin
2 Service d'Endocrinologie
3 U1162 - Génomique Fonctionnelle des Tumeurs Solides
4 Medizinische Klinik und Poliklinik IV
5 Comprehensive Heart Failure Center
6 Endocrine and Diabetes Unit
7 UM3 (UMR 8104 / U1016) - Institut Cochin
8 AIM - UMR 7158 - UMR E 9005 - Astrophysique Interactions Multi-échelles
9 CIT - "Cartes d'Identité des Tumeurs " program
10 Erasmus MC Cancer Institute, Erasmus MC
11 Reinier de Graaf Hospital
12 Institut National de la Santé et de la Recherche Médicale
13 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
14 Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique
15 Médecine nucléaire
Département d'imagerie médicale [Gustave Roussy]
16 Hypertension unit Assistance Publique–Hôpitaux de Paris
17 Pôle Endocrinologie-Diabétologie Adultes-Enfants
18 CIT - Programme"Cartes d'Identité des Tumeurs "
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 β-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.
Keywords : MicroRNAs/metabolism Male adolescent Adrenal Cortex Neoplasms/*genetics Adrenocortical Carcinoma/*genetics Adult Aged 80 and over Cohort Studies DNA Methylation DNA Mutational Analysis Exome Female Gene Expression Profiling Gene Expression Regulation Neoplastic Genomics Humans Loss of Heterozygosity Middle Aged Multigene Family Mutation Polymorphism Single Nucleotide Prognosis Telomere/ultrastructure Ubiquitin-Protein Ligases/metabolism Young Adult beta Catenin/metabolism
Type de document :
Article dans une revue
Nature Genetics, Nature Publishing Group, 2014, 46 (6), pp.607-12. 〈10.1038/ng.2953〉
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http://hal.univ-brest.fr/hal-01255809
Contributeur : Ghislaine Calvez <>
Soumis le : jeudi 14 janvier 2016 - 09:40:27
Dernière modification le : mercredi 19 septembre 2018 - 01:32:23

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Guillaume Assié, Eric Letouzé, Martin Fassnacht, Anne Jouinot, Windy Luscap, et al.. Integrated genomic characterization of adrenocortical carcinoma.. Nature Genetics, Nature Publishing Group, 2014, 46 (6), pp.607-12. 〈10.1038/ng.2953〉. 〈hal-01255809〉

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