Integrated genomic characterization of adrenocortical carcinoma

Guillaume Assié¹, Eric Letouzé², Martin Fassnacht³, Anne Jouinot⁴, Windy Luscap⁴, Olivia Barreau⁵, Hanin Omeiri⁴, Stéphanie Rodriguez⁴, Karine Perlemoine⁴, Fernande René-Corail⁴, Nabila Elarouci⁶, Silviu Sbiera⁷, Matthias Kroiss⁸, Bruno Allolio⁹, Jens Waldmann¹⁰, Marcus Quinkler¹¹, Massimo Mannelli¹², Franco Mantero¹³, Thomas Papathomas¹⁴, Ronald De Krijger¹⁴, Antoine Tabarin¹⁵, Véronique Kerlan¹⁶, Eric Baudin¹⁷, Frédérique Tissier¹⁸, Bertrand Dousset¹⁹, Lionel Groussin⁵, Laurence Amar²⁰, Eric Clauser²¹, Xavier Bertagna²², Bruno Ragazzon⁴, Felix Beuschlein²³, Rossella Libé²², Aurélien de Reyniès², Jérôme Bertherat²⁴

Affiliations

¹ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris 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].
² 1] Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France. [2].
³ 1] Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, University of Munich, Munich, Germany. [2] Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital of Würzburg, Würzburg, Germany. [3] Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
⁴ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
⁵ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] Center for Rare Adrenal Diseases, Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
⁶ Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France.
⁷ 1] Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, University of Munich, Munich, Germany. [2] Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital of Würzburg, Würzburg, Germany.
⁸ Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
⁹ Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital of Würzburg, Würzburg, Germany.
¹⁰ Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
¹¹ Department of Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine, Berlin, Germany.
¹² Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
¹³ Endocrinology Unit, Department of Medicine, University of Padova, Padova, Italy.
¹⁴ Department of Pathology, Josephine Nefkens Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
¹⁵ 1] Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Bordeaux, Bordeaux, France. [2] Rare Adrenal Cancer Network COMETE, Paris, France.
¹⁶ 1] Rare Adrenal Cancer Network COMETE, Paris, France. [2] Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Brest, Brest, France.
¹⁷ 1] Rare Adrenal Cancer Network COMETE, Paris, France. [2] Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, Université Paris-Sud, Villejuif, France.
¹⁸ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpétrière, Pierre et Marie Curie Université, Paris, France.
¹⁹ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris 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] Department of Digestive and Endocrine Surgery, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
²⁰ Hypertension Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
²¹ Oncogenetic Laboratory, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
²² 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris 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] Rare Adrenal Cancer Network COMETE, Paris, France.
²³ Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, University of Munich, Munich, Germany.
²⁴ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris 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] Rare Adrenal Cancer Network COMETE, Paris, France. [6].

PMID: 24747642
DOI: 10.1038/ng.2953

Integrated genomic characterization of adrenocortical carcinoma

Guillaume Assié et al. Nat Genet. 2014 Jun.

. 2014 Jun;46(6):607-12.

doi: 10.1038/ng.2953. Epub 2014 Apr 20.

Authors

Affiliations

¹ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris 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].
² 1] Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France. [2].
³ 1] Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, University of Munich, Munich, Germany. [2] Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital of Würzburg, Würzburg, Germany. [3] Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
⁴ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
⁵ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] Center for Rare Adrenal Diseases, Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
⁶ Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France.
⁷ 1] Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, University of Munich, Munich, Germany. [2] Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital of Würzburg, Würzburg, Germany.
⁸ Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
⁹ Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital of Würzburg, Würzburg, Germany.
¹⁰ Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
¹¹ Department of Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine, Berlin, Germany.
¹² Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
¹³ Endocrinology Unit, Department of Medicine, University of Padova, Padova, Italy.
¹⁴ Department of Pathology, Josephine Nefkens Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
¹⁵ 1] Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Bordeaux, Bordeaux, France. [2] Rare Adrenal Cancer Network COMETE, Paris, France.
¹⁶ 1] Rare Adrenal Cancer Network COMETE, Paris, France. [2] Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Brest, Brest, France.
¹⁷ 1] Rare Adrenal Cancer Network COMETE, Paris, France. [2] Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, Université Paris-Sud, Villejuif, France.
¹⁸ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpétrière, Pierre et Marie Curie Université, Paris, France.
¹⁹ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris 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] Department of Digestive and Endocrine Surgery, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
²⁰ Hypertension Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
²¹ Oncogenetic Laboratory, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
²² 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris 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] Rare Adrenal Cancer Network COMETE, Paris, France.
²³ Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, University of Munich, Munich, Germany.
²⁴ 1] INSERM U1016, Institut Cochin, Paris, France. [2] CNRS UMR 8104, Paris, France. [3] Université Paris 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] Rare Adrenal Cancer Network COMETE, Paris, France. [6].

PMID: 24747642
DOI: 10.1038/ng.2953

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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References

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Integrated genomic characterization of adrenocortical carcinoma

Affiliations

Integrated genomic characterization of adrenocortical carcinoma

Authors

Affiliations

Abstract

References

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MeSH terms

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Associated data

LinkOut - more resources

Full Text Sources

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Medical

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