Integrated genomic characterization of adrenocortical carcinoma

Menée initialement à partir d'échantillons tumoraux prélevés sur 45 patients atteints d'un carcinome corticosurrénalien, puis sur une cohorte complémentaire de 77 patients, cette étude identifie, sur la base d'une analyse génomique intégrée, deux sous-groupes associés à une forme agressive ou indolente de la maladie

Résumé en anglais

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 ligase6, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the