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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
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.
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Submitted on : Thursday, January 14, 2016 - 9:40:27 AM
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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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