Integrated genomic characterization of adrenocortical carcinoma
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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Pan-genomic characterization of adrenocortical carcinomas has identified several other driver genes including CDKN2A, RB1, DAXX, TERT, MED12, PRKAR1A, RPL22, TERF2, CCNE1, and NF-1.
“Pan-genomic characterization of ACCs has identified several other driver genes including CDKN2A, RB1, DAXX, TERT, MED12, PRKAR1A, RPL22, TERF2, CCNE1, and NF-1 (165,168).”
From Adrenal incidentaloma (2020) · cites this paper as [165]
Mutations in ZNRF3 were identified in 21% of 123 adrenocortical carcinomas following genomic characterization.
“Mutations in this gene were identified in 21% of 123 ACCs following genomic characterization (165).”
From Adrenal incidentaloma (2020) · cites this paper as [165]
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“com/edrv CDKN2A, RB1, DAXX, TERT, MED12, PRKAR1A, RPL22, TERF2, CCNE1, and NF-1 (165,168).”
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- Authors
- Assié, G., Letouzé, E., 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., Libé, R., de Reyniès, A., & Bertherat, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Würzburg (DE)
- La Ligue Contre le Cancer (FR)
- LMU Klinikum (DE)
- Universitätsklinikum Würzburg (DE)
- Universitätsklinikum Gießen und Marburg (DE)
- Stiftung Charité (DE)
- University of Florence (IT)
- University of Padua (IT)
- Erasmus MC (NL)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- ORCID
- Assié, Guillaume
- Fassnacht, Martin
- Jouinot, Anne
- Rodriguez, Stéphanie
- Elarouci, Nabila
- Sbiera, Silviu
- Kroiss, Matthias
- Quinkler, Marcus
- Mannelli, Massimo
- Mantero, Franco
- Papathomas, Thomas
- Tabarin, Antoine
- Kerlan, Véronique
- Dousset, Bertrand
- Groussin, Lionel
- Amar, Laurence
- Ragazzon, Bruno
- Beuschlein, Felix
- Libé, Rossella
- Venue
- Nature Genetics
- Published
- 2014-04-20
- Volume
- 46
- Issue
- 6
- Pages
- 607-612
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2098622295
- Cited by
- 732
- References
- 76
- Citations by year
- 2026: 34 · 2025: 48 · 2024: 43 · 2023: 50 · 2022: 74 · 2021: 89 · 2020: 62 · 2019: 64 · 2018: 63 · 2017: 55 · 2016: 61 · 2015: 69 · 2014: 18
- FWCI
- 66.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- HAL (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- adrenocortical carcinoma, driver genes, ZNRF3, DAXX, telomerase reverse transcriptase, MED12, molecular subtypes, prognosis, tumor suppressor, β-catenin signaling, DNA methylation, miRNA clusters, CTNNB1, TP53, CDKN2A, RB1, MEN1, E3 ubiquitin ligase
- MeSH terms
- Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Aged, 80 and over, DNA Mutational Analysis, Female, Multigene Family, Humans, Male, Middle Aged, Mutation, Prognosis, Cohort Studies, Gene Expression Regulation, Neoplastic, Telomere, Adrenocortical Carcinoma, DNA Methylation, Loss of Heterozygosity, Polymorphism, Single Nucleotide, Gene Expression Profiling, Genomics, MicroRNAs, Ubiquitin-Protein Ligases, beta Catenin, Young Adult, Exome
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