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Bruno Ragazzon Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France

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Guillaume Assié Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France

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Jérôme Bertherat Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France
Institut Cochin, Inserm, Department of Endocrinology, Université Paris Descartes, CNRS (UMR 8104), 75014 Paris, France

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Introduction Unilateral adrenocortical tumors (ACT) are either benign (adenomas) or malignant (cancers). Adenomas are rather common, and are frequently found as incidental tumors ( Grumbach et al . 2003 ). The clinical manifestations of ACTs may be

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Fidéline Bonnet-Serrano Institut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris, France
Hormonal Biology Laboratory, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Jérôme Bertherat Institut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris, France
Department of Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Introduction Adrenocortical tumors can be unilateral or bilateral, secreting or non-secreting various types of adrenal steroids depending on tumor type. Unilateral adrenocortical tumors are frequent in the general population; most of them are

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Rossella Libè
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Amato Fratticci
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Jérôme Bertherat
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Introduction Adrenocortical tumors, mostly benign adenomas, are frequent in the general population and nowadays most often found incidentally ( Grumbach et al. 2003 ). By contrast, adrenocortical cancer (ACC) is rare, with an

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Stefano Caramuta Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Linkiat Lee Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Deniz M Özata Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Pinar Akçakaya Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Hong Xie Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Anders Höög Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Jan Zedenius Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Martin Bäckdahl Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Catharina Larsson Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Weng-Onn Lui Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden
Departments of Oncology-Pathology, Molecular Medicine and Surgery, Cancer Center Karolinska (CCK), Department of Breast and Endocrine Surgery, Karolinska Institutet, Stockholm, Sweden

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Introduction Adrenocortical tumors are detected in up to 7% of the population and are often found as incidental tumors ( Hammarstedt et al . 2010 ). The majority of these tumors are adenomas while only a small proportion are classified as

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Michael Solarski Division of Neurosurgery, Department of Surgery, St. Michael’s Hospital, Toronto, Ontario, Canada

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Fabio Rotondo Division of Pathology, Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada

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William D Foulkes Department of Human Genetics, Medicine and Oncology, McGill University, Montreal, Quebec, Canada
Lady Davis Institute, Jewish General Hospital and Research Institute, McGill University Health Centre, Montreal, Quebec, Canada

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John R Priest Department of Medicine, Minneapolis, Minnesota, USA

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Luis V Syro Department of Neurosurgery, Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia

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Henriett Butz Molecular Medicine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary

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Michael D Cusimano Division of Neurosurgery, Department of Surgery, St. Michael’s Hospital, Toronto, Ontario, Canada

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Kalman Kovacs Division of Pathology, Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada

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performed in order to determine if the DICER1 is a viable therapeutic target. DICER1 mutations in medullary and adrenocortical tumors In the last decade, genomic approaches have been successfully applied to adrenocortical and medullary tumors

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Sandra Rodríguez-Rodero Endocrinology and Nutrition Service Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain

Cancer Epigenetics Laboratory Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain

Department of Immunology and Oncology National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain
Endocrinology and Nutrition Service Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain

Cancer Epigenetics Laboratory Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain

Department of Immunology and Oncology National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain

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Elías Delgado-Álvarez Endocrinology and Nutrition Service Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain

Cancer Epigenetics Laboratory Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain

Department of Immunology and Oncology National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain

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Agustín F Fernández Endocrinology and Nutrition Service Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain

Cancer Epigenetics Laboratory Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain

Department of Immunology and Oncology National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain

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Juan L Fernández-Morera Endocrinology and Nutrition Service Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain

Cancer Epigenetics Laboratory Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain

Department of Immunology and Oncology National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain

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Edelmiro Menéndez-Torre Endocrinology and Nutrition Service Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain

Cancer Epigenetics Laboratory Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain

Department of Immunology and Oncology National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain

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Mario F Fraga Endocrinology and Nutrition Service Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain

Cancer Epigenetics Laboratory Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain

Department of Immunology and Oncology National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain
Endocrinology and Nutrition Service Hospital Universitario Central de Asturias, Av. Julian Clavería s/n, 33006 Oviedo, Spain

Cancer Epigenetics Laboratory Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain

Department of Immunology and Oncology National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain

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hormones and include adrenal gland tumor (adrenocortical carcinoma, ACC), islet cell tumors (gastrinoma, VIPoma, glucagonoma, and somatostatinoma), neuroendocrine tumors (such as pheochromocytoma), parathyroid and thyroid carcinomas, among others. In the

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Vassiliki Kotoula
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Elias Sozopoulos Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece

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Helen Litsiou Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece

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Galinos Fanourakis Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece

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Triantafyllia Koletsa
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Gerassimos Voutsinas Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece

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Sophia Tseleni-Balafouta Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece

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Constantine S Mitsiades Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece
Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece

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Axel Wellmann Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece

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Nicholas Mitsiades Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece
Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece
Department of Pathology, Department of Pathology, Laboratory of Environmental Mutagenesis and Carcinogenesis, Department of Medical Oncology, Department of Medicine, Institute of Pathology, Memorial Sloan-Kettering Cancer Center, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece

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Introduction Adrenocortical carcinoma is a rare endocrine tumor with overall poor prognosis. Complete surgical resection is the only potentially curative treatment, but even then, distant recurrences are common. Adrenocortical carcinoma is resistant

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Thomas G Papathomas Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Lindsey Oudijk Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Ellen C Zwarthoff Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Edward Post Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Floor A Duijkers Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Max M van Noesel Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Leo J Hofland Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Patrick J Pollard Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Eamonn R Maher Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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David F Restuccia Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Richard A Feelders Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Gaston J H Franssen Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Henri J Timmers Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Stefan Sleijfer Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Wouter W de Herder Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Ronald R de Krijger Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands
Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Winand N M Dinjens Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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Esther Korpershoek Department of Pathology Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

Department of Pediatric Oncology–Hematology Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

Sector of Endocrinology Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, UK

Department of Medical Genetics University of Cambridge, Cambridge, UK

Department of Surgery Erasmus MC, Rotterdam, The Netherlands

Division of Endocrinology Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Department of Medical Oncology Erasmus MC, Rotterdam, The Netherlands

Department of Pathology Reinier de Graaf Hospital, Delft, The Netherlands

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normal adrenocortical tissue. No RNA was available to test the remaining tumors endowed with the C228T and C250T mutations. Statistical analysis Statistical analysis was performed using SPSS (IBM SPPS Statistics, version 20) on a series of 218 tumors

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Helene Myrtue Nielsen Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France
Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Alexandre How-Kit Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Carole Guerin Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Frederic Castinetti Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Hans Kristian Moen Vollan Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France
Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France
Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Catherine De Micco Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Antoine Daunay Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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David Taieb Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Peter Van Loo Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France
Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Celine Besse Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Vessela N Kristensen Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France
Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France
Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Lise Lotte Hansen Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Anne Barlier Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Frederic Sebag Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Jörg Tost Laboratory for Functional Genomics, Institute of Biomedicine, Endocrine and Metabolic Surgery Department, Department of Endocrinology, Department of Genetics, Division of Surgery, The K G Jebsen Center for Breast Cancer Research, Pathology Department, Nuclear Endocrine Imaging and Treatment Department, Cancer Research UK, Department of Human Genetics, Genotyping Facilities, Department of Clinical Molecular Biology (EpiGen), Laboratory of Molecular Biology, Laboratory for Epigenetics and Environment, Fondation Jean Dausset – Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

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Introduction Tumors developing in the adrenal gland include a heterogeneous group of adrenocortical and adrenomedullary malignancies ( Brunt & Moley 2001 , Grumbach et al . 2003 ). Most adrenal tumors are benign and non-hormone producing. However

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Meenu Jain Endocrine Oncology Branch, National Center for Advancing Translational Sciences, National Cancer Institute

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Lisa Zhang Endocrine Oncology Branch, National Center for Advancing Translational Sciences, National Cancer Institute

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Mei He Endocrine Oncology Branch, National Center for Advancing Translational Sciences, National Cancer Institute

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Ya-Qin Zhang Endocrine Oncology Branch, National Center for Advancing Translational Sciences, National Cancer Institute

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Min Shen Endocrine Oncology Branch, National Center for Advancing Translational Sciences, National Cancer Institute

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Electron Kebebew Endocrine Oncology Branch, National Center for Advancing Translational Sciences, National Cancer Institute

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human adrenocortical tissue specimens were analyzed (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 ACCs). The clinical protocol was approved by the institutional review board and written informed consent was obtained. The inclusion

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