| Literature DB >> 24747642 |
Guillaume Assié1, Eric Letouzé2, Martin Fassnacht3, Anne Jouinot4, Windy Luscap4, Olivia Barreau5, Hanin Omeiri4, Stéphanie Rodriguez4, Karine Perlemoine4, Fernande René-Corail4, Nabila Elarouci6, Silviu Sbiera7, Matthias Kroiss8, Bruno Allolio9, Jens Waldmann10, Marcus Quinkler11, Massimo Mannelli12, Franco Mantero13, Thomas Papathomas14, Ronald De Krijger14, Antoine Tabarin15, Véronique Kerlan16, Eric Baudin17, Frédérique Tissier18, Bertrand Dousset19, Lionel Groussin5, Laurence Amar20, Eric Clauser21, Xavier Bertagna22, Bruno Ragazzon4, Felix Beuschlein23, Rossella Libé22, Aurélien de Reyniès2, Jérôme Bertherat24.
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.Entities:
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Year: 2014 PMID： 24747642 DOI： 10.1038/ng.2953
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330