Medline ® Abstract for Reference 74
of 'Clinical presentation and evaluation of adrenocortical tumors'
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Integrated genomic characterization of adrenocortical carcinoma.
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AssiéG, LetouzéE, Fassnacht M, Jouinot A, Luscap W, Barreau O, Omeiri H, Rodriguez S, Perlemoine K, René-Corail F, Elarouci N, Sbiera S, Kroiss M, Allolio B, Waldmann J, Quinkler M, Mannelli M, Mantero F, Papathomas T, De Krijger R, Tabarin A, Kerlan V, Baudin E, Tissier F, Dousset B, Groussin L, Amar L, Clauser E, Bertagna X, Ragazzon B, Beuschlein F, LibéR, de Reyniès A, Bertherat J
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Nat Genet. 2014;46(6):607. Epub 2014 Apr 20.
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 theβ-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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1]INSERM U1016, Institut Cochin, Paris, France. [2]CNRS UMR 8104, Paris, France. [3]UniversitéParis Descartes, Sorbonne Paris Cité, Paris, France. [4]Center for Rare Adrenal Diseases, Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France. [5].
PMID