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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 and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

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improve outcomes. The rearranged during transfection (RET) proto-oncogene represents a paradigm for the power of molecular medicine to drive changes in diagnosis and patient management that alter disease outcomes and patient quality of life. Originally

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Barbora Bulanova Pekova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Vlasta Sykorova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Karolina Mastnikova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Eliska Vaclavikova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Jitka Moravcova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Petr Vlcek Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Lucie Lancova Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Petr Lastuvka Departments of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Rami Katra Department of Ear, Nose and Throat, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Petr Bavor Department of Surgery, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Daniela Kodetova Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

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Martin Chovanec Department of Otorhinolaryngology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic

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Jana Drozenova Department of Pathology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic

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Radoslav Matej Department of Pathology, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic

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Jaromir Astl Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine and Military University Hospital, Prague, Czech Republic

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Jiri Hlozek Department of Otorhinolaryngology and Maxillofacial Surgery, 3rd Faculty of Medicine and Military University Hospital, Prague, Czech Republic

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Petr Hrabal Department of Pathology, Military University Hospital, Prague, Czech Republic

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Josef Vcelak Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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Bela Bendlova Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

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genetic alterations found in thyroid cancer includes different types of mutations: somatic point mutations, indels, copy number alterations, and fusion genes ( Nikiforov 2011 ). Among the fusion genes, the most common and best known are RET (rearranged

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Maria Domenica Castellone Istituto di Endocrinologia ed Oncologia Sperimentale del CNR ‘G. Salvatore’, Naples, Italy

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Rosa Marina Melillo Istituto di Endocrinologia ed Oncologia Sperimentale del CNR ‘G. Salvatore’, Naples, Italy
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University of Naples ‘Federico II’, Naples, Italy

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be associated with pheochromocytoma (PC) and parathyroid adenoma/carcinoma in MEN2A or with PC, mucosal neuromas and marphanoid habitus in MEN2B. Activating mutations in the REarranged during Transfection ( RET ) proto-oncogene are responsible for the

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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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. 2006 ). The RET oncogene was first described in 1985 by Takahashi et al . (1985) . Since then, over 100 genetic alterations involving RET have been found in patients with sporadic and hereditary MTCs. RET mutation occurs in virtually all cases

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Jie Cai School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Lin Li School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Lei Ye School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Xiaohua Jiang School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Liyun Shen School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Zhibo Gao School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Weiyuan Fang School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Fengjiao Huang School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Tingwei Su School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Yulin Zhou School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Weiqing Wang School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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Guang Ning School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China
School of Medicine, BGI-Shenzhen, Laboratory for Endocrine and Metabolic Diseases of Institute of Health Science, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, #197 Ruijin 2nd Road, Shanghai 200025 People's Republic of China

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endocrine neoplasms has been observed between and within families. In the early 1990s, direct DNA analysis found mutations in the rearranged during transfection ( RET ) proto-oncogene as the genetic cause of MEN2A ( Mulligan et al . 1993 , Asai et al

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Raffaele Ciampi
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Thomas J Giordano
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Kathryn Wikenheiser-Brokamp
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Ronald J Koenig
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Yuri E Nikiforov
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Introduction Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and accounts for ~80% of all thyroid malignancies ( Hundahl et al. 2000 ). Genetic alterations along the RET/RAS/BRAF/ MAPK signaling

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Teresa Ramone Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Cristina Romei Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Raffaele Ciampi Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Roberta Casalini Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Angelo Valetto Department of Laboratory Medicine, Section of Cytogenetics, University Hospital of Pisa, Pisa, Italy

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Veronica Bertini Department of Laboratory Medicine, Section of Cytogenetics, University Hospital of Pisa, Pisa, Italy

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Francesco Raimondi Laboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Pisa, Italy

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Anthony Onoja Laboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Pisa, Italy

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Alessandro Prete Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Antonio Matrone Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Carla Gambale Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Paolo Piaggi Department of Information Engineering, University of Pisa, Pisa, Italy

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Liborio Torregrossa Department of Surgical, Medical, Molecular Pathology and Critical Area, Unit of Pathology, University Hospital of Pisa, Pisa, Italy

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Clara Ugolini Department of Surgical, Medical, Molecular Pathology and Critical Area, Unit of Pathology, University Hospital of Pisa, Pisa, Italy

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Rossella Elisei Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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the same hospital. For the purpose of this study, we selected 40 MTC cases whose mutation profile was previously identified: 23 cases were positive and 17 negative for RET somatic mutation. The present study was approved by the Institutional Review

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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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Introduction The RET receptor tyrosine kinase is required for the development of multiple human tissues ( Mulligan 2014 ). Under normal conditions, RET is activated by binding a glial cell line-derived neurotrophic factor (GDNF) family ligand

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Valtter B Virtanen
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Eero Pukkala Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland
Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland

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Reetta Kivisaari Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland

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Perttu P Salo Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland

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Antti Koivusalo
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Johanna Arola Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland

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Päivi J Miettinen Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland
Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland

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Risto J Rintala
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Markus Perola Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland
Section of Pediatric Surgery, Finnish Cancer Registry, Tampere School of Health Sciences, Helsinki Medical Imaging Center, Department of Pathology, Section of Pediatrics, Program of Molecular Neurology, The Estonian Genome Center, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, PL 281, FI-00029 HUS Helsinki, Finland

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Mikko P Pakarinen
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neurocristopathies in HD, including familial medullary thyroid carcinoma (MTC), multiple endocrine neoplasia (MEN) syndromes, and neuroblastoma ( Le Douarin & Kalcheim 1999 ). Currently, at least ten genes are known to be involved in pathogenesis of HD. The RET

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J Di Cristofaro
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V Vasko
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V Savchenko
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S Cherenko
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A Larin
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M D Ringel
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M Saji
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M Marcy
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J F Henry
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P Carayon
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C De Micco
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found among liquidators exposed during recovery work from April to July 1986, when the risk of internal irradiation of the thyroid with incorporated 131 I was greatest. Occurrence of ret oncogene rearrangements involving several different

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