Integrated genomic characterization of adrenocortical carcinoma - PubMed (original) (raw)

doi: 10.1038/ng.2953. Epub 2014 Apr 20.

Eric Letouzé 2, Martin Fassnacht 3, Anne Jouinot 4, Windy Luscap 4, Olivia Barreau 5, Hanin Omeiri 4, Stéphanie Rodriguez 4, Karine Perlemoine 4, Fernande René-Corail 4, Nabila Elarouci 6, Silviu Sbiera 7, Matthias Kroiss 8, Bruno Allolio 9, Jens Waldmann 10, Marcus Quinkler 11, Massimo Mannelli 12, Franco Mantero 13, Thomas Papathomas 14, Ronald De Krijger 14, Antoine Tabarin 15, Véronique Kerlan 16, Eric Baudin 17, Frédérique Tissier 18, Bertrand Dousset 19, Lionel Groussin 5, Laurence Amar 20, Eric Clauser 21, Xavier Bertagna 22, Bruno Ragazzon 4, Felix Beuschlein 23, Rossella Libé 22, Aurélien de Reyniès 2, Jérôme Bertherat 24

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Integrated genomic characterization of adrenocortical carcinoma

Guillaume Assié et al. Nat Genet. 2014 Jun.

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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