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Kimberly Perez Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA

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Heather Jacene Harvard Medical School, Boston, Massachusetts, USA
Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Jason L Hornick Harvard Medical School, Boston, Massachusetts, USA
Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Chao Ma Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Nuno Vaz Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Lauren K Brais Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Holly Alexander Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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William Baddoo Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Kristina Astone Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Edward D Esplin Invitae Corporation, San Francisco, California, USA

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John Garcia Invitae Corporation, San Francisco, California, USA

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Daniel M Halperin Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Matthew H Kulke Section of Hematology and Oncology, Boston University and Boston Medical Center, Boston, Massachusetts, USA

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Jennifer A Chan Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA

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, among other genes ( Neumann et al. 2002 , Adler et al. 2008 ). SDHx mutations are found in approximately 27% of patients with advanced PHEO/PGL ( Young et al. 2002 ). Pathogenic mutations in succinate dehydrogenase subunit B ( SDHB) have been

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Ying Ni Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Spencer Seballos Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Shireen Ganapathi Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Danielle Gurin Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Benjamin Fletcher Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Joanne Ngeow Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Rebecca Nagy Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Richard T Kloos Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Matthew D Ringel Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Thomas LaFramboise Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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Charis Eng Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA
Genomic Medicine Institute Lerner Research Institute

Taussig Cancer Institute

Stanley Shalom Zielony Nursing Institute Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USA

Division of Medical Oncology National Cancer Center, Singapore 169610, Singapore

Divisions of Human Genetics

Endocrinology and Metabolism Department of Medicine

Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA

Departments of Genetics and Genome Sciences

Epidemiology and Biostatistics

CASE Comprehensive Cancer Center Case Western Reserve University, Cleveland, Ohio 44116, USA

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whether germline SDHB/C/D ( SDHx ) variants could also occur in PTEN (MIM 601728) mutation-negative CS/CS-like individuals. Indeed, we found 8–10% of such patients carry SDHx mutations ( Ni et al . 2008 , 2012 ). CS/CS-like individuals with

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Ales Vicha
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David Taieb Department of Pediatric Hematology and Oncology, Service Central de Biophysique et de Médecine Nucléaire, Département d'Oncologie Moléculaire, Program in Reproductive and Adult Endocrinology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic
Department of Pediatric Hematology and Oncology, Service Central de Biophysique et de Médecine Nucléaire, Département d'Oncologie Moléculaire, Program in Reproductive and Adult Endocrinology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic

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Karel Pacak Department of Pediatric Hematology and Oncology, Service Central de Biophysique et de Médecine Nucléaire, Département d'Oncologie Moléculaire, Program in Reproductive and Adult Endocrinology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic

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SDHx ( SDHD , SDHB , SDHC , SDHA , and SDHAF2 ) mutations and also accounts for about 30% of sporadic tumors ( Dahia et al . 2005 , Lopez-Jimenez et al . 2010 , Burnichon et al . 2011 ). The second group (cluster 2) represents tumors carrying

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Henri J L M Timmers
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Anne-Paule Gimenez-Roqueplo Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, INSERM, Endocrinology Unit, Reproductive and Adult Endocrinology Program, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, INSERM, Endocrinology Unit, Reproductive and Adult Endocrinology Program, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, INSERM, Endocrinology Unit, Reproductive and Adult Endocrinology Program, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

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Massimo Mannelli Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, INSERM, Endocrinology Unit, Reproductive and Adult Endocrinology Program, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

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Karel Pacak Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, INSERM, Endocrinology Unit, Reproductive and Adult Endocrinology Program, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

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syndromes with which sPGL is associated are multiple endocrine neoplasia type 2 ( RET mutations), von Hippel-Lindau disease ( VHL mutations), hereditary PGL/pheochromocytoma syndromes ( SDHx mutations), and rarely neurofibromatosis type 1 ( NF1 mutations

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Francesca Branzoli Paris Brain Institute - Institut du Cerveau (ICM), Center for Neuroimaging Research (CENIR), Paris, France
Sorbonne University, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France

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Betty Salgues Sorbonne University, nuclear medicine department, Pitié-Salpêtrière Hospital, Assistance -Publique Hôpitaux de Paris, Paris, France
Paris Cardiovascular Research Center (PARCC), Inserm, Paris, France

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Małgorzata Marjańska Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA

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Marie Laloi-Michelin Endocrinology department, Lariboisière Hospital, Assistance -Publique Hôpitaux de Paris, Paris, France

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Philippe Herman ENT unit, Lariboisière Hospital, Assistance -Publique Hôpitaux de Paris, Paris-Cité University, INSERM U1141, Paris, France

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Lauriane Le Collen Inserm/CNRS UMR 1283/8199, Pasteur Institute of Lille, EGID, University of Lille, Lille, France
Department of Endocrinology Diabetology, University Hospital Center of Reims, Reims, France
Department of Genetic, University Hospital Center of Reims, Reims, France

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Brigitte Delemer Department of Endocrinology Diabetology, University Hospital Center of Reims, Reims, France
CRESTIC EA 3804, University of Reims Champagne Ardenne, UFR Sciences Exactes et Naturelles, Moulin de La Housse, BP 1039, Reims, France

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Julien Riancho AP-HP, Hôpital Européen Georges Pompidou, Hypertension Unit, and Reference centre for rare adrenal diseases, Paris, France

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Emmanuelle Kuhn Pituitary Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Christel Jublanc Pituitary Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Nelly Burnichon Département de médecine génomique des tumeurs et des cancers, AP-HP, Hôpital Européen Georges Pompidou, Paris, France
Université Paris Cité, Inserm, PARCC, Paris, France

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Laurence Amar AP-HP, Hôpital Européen Georges Pompidou, Hypertension Unit, and Reference centre for rare adrenal diseases, Paris, France
Université Paris Cité, Inserm, PARCC, Paris, France

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Judith Favier Université Paris Cité, Inserm, PARCC, Paris, France

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Anne-Paule Gimenez-Roqueplo Département de médecine génomique des tumeurs et des cancers, AP-HP, Hôpital Européen Georges Pompidou, Paris, France
Université Paris Cité, Inserm, PARCC, Paris, France

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Alexandre Buffet Département de médecine génomique des tumeurs et des cancers, AP-HP, Hôpital Européen Georges Pompidou, Paris, France
Université Paris Cité, Inserm, PARCC, Paris, France

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Charlotte Lussey-Lepoutre Sorbonne University, nuclear medicine department, Pitié-Salpêtrière Hospital, Assistance -Publique Hôpitaux de Paris, Paris, France
Paris Cardiovascular Research Center (PARCC), Inserm, Paris, France

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), related to succinate dehydrogenase ( SDHx) pathogenic variants ( Xekouki et al. 2015 ) in about 40% of cases. Genes encoding SDH enzyme and its assembly factor, collectively referred to as SDHx genes ( SDHA, SDHB, SDHC, SDHD, and SDHAF2 ), are the

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Priya Gopie Massey Cancer Center, VCU School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

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Lin Mei Massey Cancer Center, VCU School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

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Anthony C Faber Phillips Institute for Oral Health Research, VCU School of Dentistry and Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA

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Steven R Grossman Massey Cancer Center, VCU School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

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Steven C Smith Departments of Pathology and Surgery, VCU School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

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Sosipatros A Boikos Massey Cancer Center, VCU School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

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been found to harbor mutations in other genes, including platelet-derived growth factor (PDGF) receptor alpha ( PDGFRA ), succinate dehydrogenase complex subunits ( SDHx ), neurofibromin 1 ( NF1 ), B-raf proto-oncogene ( BRAF ) and most recently

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M Montani
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A M Schmitt
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S Schmid
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T Locher
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P Saremaslani
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P U Heitz
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P Komminoth
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A Perren
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in all informative exons of SDHB , SDHC and SDHD . However, 12 of 35 patients (34.3%) showed SDHx germline alterations, present in neoplastic as well as in non-neoplastic tissue. SDHB In intron 2 of SDHB , germline

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Paraskevi Xekouki Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Inter-Institute Pediatric Endocrinology Program, National Institutes of Health (NIH), Building 10, CRC, Room 1-3330, 10 Center Drive, MSC1103, Bethesda, Maryland 20892, USA

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Constantine A Stratakis Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Inter-Institute Pediatric Endocrinology Program, National Institutes of Health (NIH), Building 10, CRC, Room 1-3330, 10 Center Drive, MSC1103, Bethesda, Maryland 20892, USA

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holotetramer to the membrane and serve as the ubiquinone site ( Oyedotun & Lemire 2004 , Kantorovich & Pacak 2010 ). Syndromes related to SDHx mutations The discovery that mutations in genes coding for the subunits SDHB , SDHC , and SDHD were responsible

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Maya B Lodish
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Karen T Adams Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Thanh T Huynh Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Tamara Prodanov Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Alex Ling Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Clara Chen Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Suzanne Shusterman Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Camilo Jimenez Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Maria Merino Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Marybeth Hughes Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Kendall W Cradic Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Dragana Milosevic Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Ravinder J Singh Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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Constantine A Stratakis
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Karel Pacak Section on Endocrinology and Genetics and Pediatric Endocrinology Program, Reproductive Biology and Adult Endocrinology Program, Department of Diagnostic Radiology, Department of Pediatric Oncology, The University of Texas M.D. Anderson Cancer Center, Pathology, Surgery, Department of Laboratory Medicine and Pathology, Program on Developmental Endocrinology and Genetics (PDEGEN), National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 10, CRC, 10 Center Drive, Room 1-3330, Bethesda, Maryland 20892, USA

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). From an initial observation of two patients with Zuckerkandl organ tumors who had SDHx mutations, we searched our clinical database for other patients with tumors involving this organ; we then tested the DNA of these patients retrospectively for

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Arthur Varoquaux Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Yann le Fur Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Alessio Imperiale Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France
Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Antony Reyre Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Marion Montava Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Nicolas Fakhry Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Izzie-Jacques Namer Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France
Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Guy Moulin Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Karel Pacak Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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Maxime Guye Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France
Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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David Taïeb Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France
Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France
Department of Medical Imaging, CNRS, Department of Biophysics and Nuclear Medicine, ICube, Department of Otorhinolaryngology–Head and Neck Surgery, Department of Otorhinolaryngology–Head and Neck Surgery, Program in Reproductive and Adult Endocrinology, Department of Nuclear Medicine, Biophysics and Nuclear Medicine, INSERM, La Timone University Hospital, Aix‐Marseille University, Marseille, France

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in one of the succinate dehydrogenase (SDH) subunit genes (collectively referred to as SDHx ) ( Baysal et al . 2002 , Neumann et al . 2009 , Piccini et al . 2012 , Martucci & Pacak 2014 ). The SDH complex (also named mitochondrial complex II

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