Skip to Main content Skip to Navigation
New interface
Journal articles

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 7 Karine Perlemoine 7 Fernande René-Corail 1 Nabila Elarouci 8 Silviu Sbiera 4, 6 Matthias Kroiss Bruno Allolio 5, 6 Jens Waldmann Marcus Quinkler Massimo Mannelli Franco Mantero Thomas Papathomas Ronald de Krijger 9, 10 Antoine Tabarin 11 Véronique Kerlan 12 Eric Baudin 13, 14 Frédérique Tissier 7 Bertrand Dousset Lionel Groussin Laurence Amar 15 Eric Clauser Xavier Bertagna 1, 16 Bruno Ragazzon Felix Beuschlein 4 Rossella Libé Aurélien de Reyniès 17 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 IC UM3 (UMR 8104 / U1016) - Institut Cochin
8 CIT - "Cartes d'Identité des Tumeurs " program
9 Erasmus MC - Erasmus University Medical Center [Rotterdam]
10 Reinier de Graaf Hospital
11 INSERM - Institut National de la Santé et de la Recherche Médicale
12 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
13 Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique
14 Médecine nucléaire
Département d'imagerie médicale [Gustave Roussy]
15 Hypertension unit Assistance Publique–Hôpitaux de Paris
16 Pôle Endocrinologie-Diabétologie Adultes-Enfants
17 CIT - (le 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 : 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 Male MicroRNAs/metabolism Middle Aged Multigene Family Mutation Polymorphism Single Nucleotide Prognosis Telomere/ultrastructure Ubiquitin-Protein Ligases/metabolism Young Adult beta Catenin/metabolism
Document type :
Journal articles
Complete list of metadata
https://hal.univ-brest.fr/hal-01255809
Contributor : Ghislaine Calvez Connect in order to contact the contributor
Submitted on : Thursday, January 14, 2016 - 9:40:27 AM
Last modification on : Friday, December 2, 2022 - 4:15:40 PM

Identifiers

Collections

UNIV-BREST | UNIV-PARIS7 | UNIV-PARIS13 | CNRS | FNCLCC | IGR | GETBO | UNIV-PARIS-SACLAY | IBSAM | SORBONNE-PARIS-NORD | UNIV-PARIS | UP-SANTE | PHYSENDO

Citation

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

Export

BibTeX TEI DC DCterms EndNote Datacite

Share

Metrics

Record views

256