Integrated genomic characterization of adrenocortical carcinoma. - Université de Bretagne Occidentale Access content directly
Journal Articles Nature Genetics Year : 2014

Integrated genomic characterization of adrenocortical carcinoma.

Guillaume Assié
Eric Letouzé
Anne Jouinot
Windy Luscap
  • Function : Author
Hanin Omeiri
  • Function : Author
Matthias Kroiss
Jens Waldmann
  • Function : Author
Marcus Quinkler
Massimo Mannelli
  • Function : Author
Franco Mantero
  • Function : Author
Thomas Papathomas
  • Function : Author
Bertrand Dousset
Lionel Groussin
  • Function : Author
Eric Clauser
  • Function : Author
Bruno Ragazzon
Felix Beuschlein
Rossella Libé
  • Function : Author

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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hal-01255809 , version 1 (14-01-2016)

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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⟩
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