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Margarida M Moura Unidade de Investigação em Patobiologia Molecular (UIPM), Serviço de Endocrinologia, Clínica Universitária de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal

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Branca M Cavaco Unidade de Investigação em Patobiologia Molecular (UIPM), Serviço de Endocrinologia, Clínica Universitária de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal

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Valeriano Leite Unidade de Investigação em Patobiologia Molecular (UIPM), Serviço de Endocrinologia, Clínica Universitária de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal
Unidade de Investigação em Patobiologia Molecular (UIPM), Serviço de Endocrinologia, Clínica Universitária de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal
Unidade de Investigação em Patobiologia Molecular (UIPM), Serviço de Endocrinologia, Clínica Universitária de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal

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mutated (total mutated samples/total samples tested) for that particular tumor type. RAS mutations have also been detected in medullary thyroid carcinomas (MTCs), and this subject will be further discussed in section ‘ RAS mutations in MTC

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Pierpaolo Trimboli Department of Nuclear Medicine and Thyroid Centre, Section of Endocrinology and Diabetology, Nuclear Medicine, Endocrine Unit, Oncology Institute of Southern Switzerland, Bellinzona, 6500, Switzerland
Department of Nuclear Medicine and Thyroid Centre, Section of Endocrinology and Diabetology, Nuclear Medicine, Endocrine Unit, Oncology Institute of Southern Switzerland, Bellinzona, 6500, Switzerland

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Ettore Seregni Department of Nuclear Medicine and Thyroid Centre, Section of Endocrinology and Diabetology, Nuclear Medicine, Endocrine Unit, Oncology Institute of Southern Switzerland, Bellinzona, 6500, Switzerland

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Giorgio Treglia Department of Nuclear Medicine and Thyroid Centre, Section of Endocrinology and Diabetology, Nuclear Medicine, Endocrine Unit, Oncology Institute of Southern Switzerland, Bellinzona, 6500, Switzerland

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Maria Alevizaki Department of Nuclear Medicine and Thyroid Centre, Section of Endocrinology and Diabetology, Nuclear Medicine, Endocrine Unit, Oncology Institute of Southern Switzerland, Bellinzona, 6500, Switzerland

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Luca Giovanella Department of Nuclear Medicine and Thyroid Centre, Section of Endocrinology and Diabetology, Nuclear Medicine, Endocrine Unit, Oncology Institute of Southern Switzerland, Bellinzona, 6500, Switzerland

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Introduction Medullary thyroid carcinoma (MTC) is a malignancy that originates from thyroid parafollicular C cells and accounts for about 5% of thyroid cancers ( Kloos et al . 2009 ). In the majority of cases (i.e., four out of every five), this

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Lucieli Ceolin Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil

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Marta Amaro da Silveira Duval Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil

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Antônio Felippe Benini Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil

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Carla Vaz Ferreira Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil

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Ana Luiza Maia Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil

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Introduction Medullary thyroid carcinoma (MTC) is a malignant tumor originating in parafollicular or C cells of the thyroid. The main secretory product of MTC is calcitonin, a specific and highly sensitive biomarker that is produced by normal

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Anna Angelousi Unit of Endocrinology, First Department of Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece

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Aimee R Hayes Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK

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Eleftherios Chatzellis Endocrinology Diabetes and Metabolism Department, 251 Hellenic Air Force and VA General Hospital, Athens, Greece

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Gregory A Kaltsas First Department of Propaedeutic Internal Medicine, Laiko Hospital, National & Kapodistrian University of Athens, Athens, Greece

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Ashley B Grossman Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK
Green Templeton College, University of Oxford, Oxford, UK
Centre for Endocrinology, Barts and the London School of Medicine, London, UK

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Introduction Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumour originating from the parafollicular or C-cells of the thyroid, capable of secreting calcitonin and carcinoembryonic antigen (CEA) ( Ceolin et al. 2019 ). It

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Libero Santarpia Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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George A Calin Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Liana Adam Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Lei Ye Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Alfredo Fusco Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Serena Giunti Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Christina Thaller Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Laura Paladini Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Xinna Zhang Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Camilo Jimenez Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Francesco Trimarchi Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Adel K El-Naggar Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Robert F Gagel Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
Departments of Endocrine Neoplasia and Hormonal Disorders, Experimental Therapeutics , Urology, Department of Oncology, Department of Pathology, Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Department of Oncology, Department of Gynecologic Oncology, Department of Endocrinology, Department of Pathology, Department of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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Introduction Medullary thyroid carcinoma (MTC) is a neuroendocrine tumour thought to originate from neural crest parafollicular C-cells. Approximately 25% of MTC cases occur in the context of autosomal dominant multiple endocrine neoplasia syndrome

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Mahdi Fallah Division of Molecular Genetic Epidemiology, Center for Primary Health Care Research, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany

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Kristina Sundquist Division of Molecular Genetic Epidemiology, Center for Primary Health Care Research, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany

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Kari Hemminki Division of Molecular Genetic Epidemiology, Center for Primary Health Care Research, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
Division of Molecular Genetic Epidemiology, Center for Primary Health Care Research, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany

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nuclear family ( Amundadottir et al . 2004 ). Medullary thyroid carcinoma (MTC) is the third most common thyroid neoplasm (3–10%) after papillary (50–80%) and follicular (10–40%) carcinomas ( Hundahl et al . 1998 , Boyle 2008 , Pacini et al . 2010

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Eric Y Lian Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

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Sarah M Maritan Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

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Jessica G Cockburn Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

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Katayoon Kasaian Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada

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Mathieu J F Crupi Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

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David Hurlbut Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

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Steven J M Jones Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
Department of Medical Genetics, University of British Columbia, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada

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Sam M Wiseman Department of Surgery, St Paul’s Hospital & University of British Columbia, Vancouver, British Columbia, Canada

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Lois M Mulligan Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada
Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

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, Romei et al . 2016 ). Constitutive activation of RET by specific point mutations gives rise to medullary thyroid carcinoma (MTC), a tumour of thyroid C-cells, as part of the familial cancer syndrome multiple endocrine neoplasia 2 (MEN2), and also occur

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Huy Gia Vuong Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan

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Toru Odate Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan

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Hanh T T Ngo Department of Pathology, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

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Thong Quang Pham Department of Pathology, Cho Ray Hospital, Ho Chi Minh City, Vietnam

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Thao T K Tran Faculty of Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

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Kunio Mochizuki Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan

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Tadao Nakazawa Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan

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Ryohei Katoh Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan

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Tetsuo Kondo Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan

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clinicopathological features of sporadic MTCs are presented in Table 2 . Table 2 Associations of RET , RAS mutation and RET M918T mutation with the clinicopathological parameters of sporadic medullary thyroid carcinoma. Clinicopathological

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Viktor Johanson
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Håkan Ahlman
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Peter Bernhardt
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Svante Jansson
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Lars Kölby
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Fredrik Persson
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Göran Stenman
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Christina Swärd
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Bo Wängberg
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Mats Stridsberg
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Ola Nilsson
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Introduction Medullary thyroid carcinoma (MTC) accounts for 5–10% of all thyroid cancer. Most cases are sporadic but about 25% occur in patients with the multiple endocrine neoplasia type 2 (MEN2) syndrome ( Brauckhoff et al

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Nabahet Ameur CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Ludovic Lacroix CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit
CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Sophie Roucan CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Véronique Roux CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Sophie Broutin CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Monique Talbot CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Corinne Dupuy CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Bernard Caillou CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Martin Schlumberger CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Jean-Michel Bidart CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit
CNRS FRE 2939, Translational Research Laboratory, Department of Nuclear Medicine and Endocrine Oncology, Functional Genomic Unit

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Introduction Medullary thyroid carcinoma (MTC) derives from thyroid C cells, a neuroendocrine cell that produces calcitonin and represents <1% of all thyroid cells ( Leboulleux et al . 2004 , Matias-Guiu et al . 2004 , Hoff & Hoff 2007 ). MTC

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