Integrated genomic characterization of adrenocortical carcinoma
Nature Genetics , Volume 46 - Issue 6 p. 607- 612
Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland1. Despite overall poor prognosis, ACC outcome is heterogeneous2,3. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes4,5 (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 ligase6, 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.
|This work was funded by the European Commission 7th Framework Programme; grant id fp7/259735 - European Network for the Study of Adrenal Tumours - Structuring clinical research on adrenal cancers in adults (ENS@T-CANCER)|
|Organisation||Department of Pathology|
Assié, G, Letouzé, E, Fassnacht, M, Jouinot, A, Luscap, W, Barreau, O, … Bertherat, J. (2014). Integrated genomic characterization of adrenocortical carcinoma. Nature Genetics, 46(6), 607–612. doi:10.1038/ng.2953