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Katharina Wang Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Ina Schütze Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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Sebastian Gulde Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany

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Nicole Bechmann Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

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Susan Richter Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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Jana Helm Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

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Michael Lauseker Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Ludwig Maximilian University of Munich, Munich, Germany

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Julian Maurer Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Astrid Reul Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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Gerald Spoettl Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Barbara Klink Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
National Center of Genetics, Laboratoire National de Santé, Dudelange, Luxembourg
German Cancer Consortium, Dresden, Germany

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Doreen William German Cancer Consortium, Dresden, Germany

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Thomas Knösel Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany

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Juliane Friemel Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland

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Michel Bihl Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland

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Achim Weber Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland

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Maria Fankhauser Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Laura Schober Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Diana Vetter Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland

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Martina Broglie Däppen Department of Otorhinolaryngology, University Hospital Zurich, Zurich, Switzerland

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Christian G Ziegler Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

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Martin Ullrich Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany

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Jens Pietzsch Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, Dresden, Germany

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Stefan R Bornstein Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

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Christian Lottspeich Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Matthias Kroiss Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany
Division of Endocrinology and Diabetes, Department of Medicine I, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

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Martin Fassnacht Division of Endocrinology and Diabetes, Department of Medicine I, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

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Vera Ursula Julia Wenter Department of Nuclear Medicine, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Roland Ladurner Department of General-, Visceral-, and Transplant-Surgery, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Constanze Hantel Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland
Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

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Martin Reincke Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Graeme Eisenhofer Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

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Ashley B Grossman Green Templeton College, University of Oxford, Oxford, UK
NET Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK

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Karel Pacak Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

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Felix Beuschlein Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany
Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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Christoph J Auernhammer Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany

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Natalia S Pellegata Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany

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Svenja Nölting Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany
Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland

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et al. 2017 , Gieldon et al. 2019 , Jiang et al. 2020 ). Therefore, around 70% of all PPGLs can be assigned to one of three main molecular clusters with different gene expression signatures and clinical behavior ( Fig. 1 ). Pseudohypoxia

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Charlotte Nys Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Yu-Lun Lee Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Heleen Roose Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Freya Mertens Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium
Department of Imaging and Pathology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Ellen De Pauw Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Hiroto Kobayashi Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium
Department of Anatomy and Structural Science, Yamagata University Faculty of Medicine, Yamagata, Japan

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Raf Sciot Department of Imaging and Pathology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Marie Bex Department of Endocrinology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Georges Versyck Department of Neurosurgery, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Steven De Vleeschouwer Department of Neurosurgery, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Johannes Van Loon Department of Neurosurgery, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Emma Laporte Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Hugo Vankelecom Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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expression of multiple pituitary stem cell markers (such as SOX2, CDH1 (encoding E-CAD), CD44 , KRT8/18 and S100A6 ) in all organoids ( Fig. 6B ), thus corroborating their stemness phenotype and confirming the findings above. The distinct PCA clustering

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Jenny Welander Department of Clinical and Experimental Medicine, Department of Surgery, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden

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Peter Söderkvist Department of Clinical and Experimental Medicine, Department of Surgery, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden

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Oliver Gimm Department of Clinical and Experimental Medicine, Department of Surgery, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden
Department of Clinical and Experimental Medicine, Department of Surgery, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden

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angiogenesis, whereas RET - and NF1 -related tumors express genes linked to an activation of kinase signaling pathways ( Eisenhofer et al . 2004 , Dahia et al . 2005 ). Interestingly, sporadic pheochromocytomas cluster into either of the two distinct

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Katarina Edfeldt Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Peyman Björklund Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Göran Åkerström Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Gunnar Westin Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Per Hellman Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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Peter Stålberg Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden

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metastases ( n =7) 11** Interferon-treated tumors ( n =2) Not interferon-treated tumors ( n =2) 7 * P <0.05, fold change 2; **fold change 1.5. To further analyze gene expression patterns, we performed unsupervised hierarchal cluster analysis using the PCA

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Karel Pacak Section of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

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Mark Kidd WREN Laboratories, Branford, Connecticut, USA

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Leah Meuter Section of Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

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Irvin M Modlin Gastroenterological and Endoscopic Surgery, Yale University School of Medicine, New Haven, Connecticut, USA

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/PGLs into cluster 1 and 2 within the neuroendocrine tumor (NET) grading classification system, as seen in the classification of gastroenteropancreatic (GEP) and bronchopulmonary (BP) tumors ( Favier et al. 2015 ). NETs of the GEP and BP systems have a

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P N Span Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine
Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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J U Rao Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine
Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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S B J Oude Ophuis Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine
Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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J W M Lenders Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine
Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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F C G J Sweep Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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P Wesseling Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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B Kusters Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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F H van Nederveen Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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R R de Krijger Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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A R M M Hermus Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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H J L M Timmers Department of Laboratory Medicine, Department of Radiation Oncology, Department of Endocrinology, Division of Vascular Medicine, Department of Pathology, Department of Pathology, Department of Internal Medicine III, Department of Internal Medicine

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). These ‘cluster 1’ tumors are distinct from ‘cluster 2’ tumors, which include RET - and NF1 -related and another subset of sporadic PGLs ( Dahia et al . 2005 ). This latter cluster is characterized by the deregulation of the RAS/RAF/MAP kinase

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Mark Kidd Wren Laboratories, 35 NE Industrial Road, Branford, Connecticut 06405, USA

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Ignat Drozdov Wren Laboratories, 35 NE Industrial Road, Branford, Connecticut 06405, USA

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Irvin Modlin Wren Laboratories, 35 NE Industrial Road, Branford, Connecticut 06405, USA

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=0.1–0.9; Wilcoxon matched-pairs signed rank test). Figure 4 Correlation between marker gene expression as a cluster ‘ome’ in tumor tissue and in peripheral blood in three different sets. (A) Gene cluster (GC) expression (individual ‘omes’) in tumor

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Jun-ichiro Suzuki Faculty of Pharmacy, Musashino University, 1-1-20 Shin-machi, Nishitokyo-shi, Tokyo 202-8585, Japan

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Yasuko Murakami Faculty of Pharmacy, Musashino University, 1-1-20 Shin-machi, Nishitokyo-shi, Tokyo 202-8585, Japan

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Keijiro Samejima Faculty of Pharmacy, Musashino University, 1-1-20 Shin-machi, Nishitokyo-shi, Tokyo 202-8585, Japan

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Kohfuku Kohda Masahiro Ohtani Faculty of Pharmacy, Musashino University, 1-1-20 Shin-machi, Nishitokyo-shi, Tokyo 202-8585, Japan

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Takami Oka Faculty of Pharmacy, Musashino University, 1-1-20 Shin-machi, Nishitokyo-shi, Tokyo 202-8585, Japan

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cultured in SFM for 3 days stopped growing, formed islet-like cell clusters (the upper panel) and produced glucagon (the lower panel). After 6 days, the size of cluster and the extent of glucagon production were substantially increased. AsPC-1 cells that

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E Puxeddu
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J A Knauf
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M A Sartor
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M Medvedovic
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(14 out of 86 with greater than or less than 1.75-fold change) belongs to a cluster involved in the regulation of the immune response. Experimental procedures Cell lines and reagents PCCL3 cells, a clonal rat

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Fredrika Svahn Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

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Karolina Solhusløkk Höse Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

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Adam Stenman Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden

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Yaxuan Liu Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China

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Jan Calissendorff Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

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Emma Tham Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden

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Ákos Végvári Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

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Roman A Zubarev Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

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Na Wang Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden

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Reju Korah Yale Endocrine Neoplasia Laboratory, Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA

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Tobias Carling Yale Endocrine Neoplasia Laboratory, Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA
Carling Adrenal Center, Tampa, Florida, USA

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Jan Zedenius Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden

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Robert Bränström Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden

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C Christofer Juhlin Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital Stockholm, Sweden

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Catharina Larsson Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

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al. 2022 ). Based on gene expression profiling, three molecular subgroups of PPGL have been identified ( Fishbein et al. 2017 , Juhlin 2021 ). Cluster 1 tumors demonstrate a pseudohypoxia expression profile, exhibit a hypermethylation phenotype

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