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Krystallenia I Alexandraki Second Department of Surgery, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece

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Ariadni Spyroglou Second Department of Surgery, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
Clinic for Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland

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Stylianos Kykalos Second Department of Propaedeutic Surgery, Laiko Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece

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Kosmas Daskalakis Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
Endocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Georgios Kyriakopoulos Department of Pathology, Evaggelismos Hospital, Athens, Greece

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Georgios C Sotiropoulos Clinic for Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland

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Gregory A Kaltsas Endocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Ashley B Grossman Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
NET Unit, Royal Free Hospital, London, UK
Barts and the London School of Medicine, London, UK

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dedifferentiate during the course of the disease in different areas within the tumour at varying times, and that this process might represent different tumoural sub-clones. However, it is difficult to identify such an accumulation of genetic alterations in NEN

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Garcilaso Riesco-Eizaguirre Instituto de Investigaciones Biomédicas ‘Alberto Sols’,, Servicio de Endocrinología y Nutrición,, Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, Spain
Instituto de Investigaciones Biomédicas ‘Alberto Sols’,, Servicio de Endocrinología y Nutrición,, Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, Spain

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Pilar Santisteban Instituto de Investigaciones Biomédicas ‘Alberto Sols’,, Servicio de Endocrinología y Nutrición,, Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, Spain

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cell lines. In an attempt to investigate the overall occurrence of genetic alterations in the PI3K/Akt pathway in sporadic thyroid cancer, Hou et al . (2007) investigated the presence of PIK3CA copy number gain and mutation, RAS mutation and PTEN

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Avaniyapuram Kannan Murugan Division of Molecular Endocrinology, Department of Molecular Oncology, King Faisal, Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

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Abeer Al-Amr Department of Microbiology, College of Science, Female Campus, King Saud University, Riyadh, Saudi Arabia

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Mysoon M Al-Ansari Department of Microbiology, College of Science, Female Campus, King Saud University, Riyadh, Saudi Arabia
Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

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Pulicat S Manogaran Department of Stem Cell Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

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Hindi Al-Hindi Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

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Ali S Alzahrani Division of Molecular Endocrinology, Department of Molecular Oncology, King Faisal, Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

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, Europe, and East Asia. The incidence has increased annually at an average rate of 3.6%, while the annual mortality rate is increased at least 1.1% ( Morris et al. 2013 ). Genetic alterations in the MAPK (mitogen-associated protein kinase) and PI3K

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Valeria Coppola Department of Hematology, Department of Experimental Oncology, Oncology and Molecular Medicine, Istituto Superiore Sanità, viale Regina Elena 299, 00161 Rome, Italy

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Ruggero De Maria Department of Hematology, Department of Experimental Oncology, Oncology and Molecular Medicine, Istituto Superiore Sanità, viale Regina Elena 299, 00161 Rome, Italy
Department of Hematology, Department of Experimental Oncology, Oncology and Molecular Medicine, Istituto Superiore Sanità, viale Regina Elena 299, 00161 Rome, Italy

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Désirée Bonci Department of Hematology, Department of Experimental Oncology, Oncology and Molecular Medicine, Istituto Superiore Sanità, viale Regina Elena 299, 00161 Rome, Italy

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been discussed above and is summarized in Table 1 . The following description includes miRs whose alterations have been correlated with genetic alterations and which eventually result in epigenetic reprogramming, miRs acting downstream of

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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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proliferation or phosphorylation of RET receptor was observed between the transfected cell lines ( Supplementary Fig. 3 , see section on supplementary data given at the end of this article). Discussion In this study we profiled genetic alterations in matched

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Roberto Bianco
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Teresa Troiani
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Giampaolo Tortora
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Fortunato Ciardiello
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deletion in the extracellular domain that leads to constitutive activation of its tyrosine kinase (TK) domain, is the most frequently expressed EGFR genetic alteration in some cancers, like glioblastomas ( Nishikawa et al. 1994 , Moscatello et al. 1995

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Eva-Maria Duerr Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology
Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Yusuke Mizukami Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology
Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Aylwin Ng Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Ramnik J Xavier Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology
Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology
Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Hirotoshi Kikuchi Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology
Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Vikram Deshpande Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Andrew L Warshaw  Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Jonathan Glickman Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Matthew H Kulke Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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Daniel C Chung Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology
Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology
Gastrointestinal Unit, Department of Medicine, Cancer Center, Center for Computational and Integrative Biology, Department of Surgery, Department of Pathology, Department of Adult Oncology

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/or metastases Any >30% Yes It is also uncertain how similar the genetic alterations are that underlie PNETs and GI-NETs, and whether they can be distinguished on a molecular level. Although there are important differences in their clinical behavior, they are

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Xuguang Zhu Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Dong Wook Kim Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Li Zhao Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Mark C Willingham Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Sheue-yann Cheng Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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the thyroid tumors of the Thrb PV/PV mouse. Still, it is known that a reduced level of the PTEN gene due to methylation or other epigenetic silencing occurs in close association with activating genetic alterations of the PI3K-AKT pathway

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Sock Hoai Chan Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore, Singapore

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Joanne Ngeow Division of Medical Oncology, Cancer Genetics Service, National Cancer Centre Singapore, Singapore
Oncology Academic Clinical Program, Duke-NUS Medical School Singapore, Singapore

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Introduction Genomic instability is a hallmark of human cancers ( Negrini et al. 2010 ). It refers to the increased frequency of accruing genetic alterations, ranging from single nucleotide mutations to whole chromosome changes such as

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Christina M Knippler Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA

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Motoyasu Saji Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA

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Neel Rajan College of Arts and Sciences, The Ohio State University, Columbus, Ohio, USA

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Kyle Porter Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA

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Krista M D La Perle Department of Veterinary Biosciences, Comparative Pathology & Mouse Phenotyping Shared Resource, The Ohio State University, Columbus, Ohio, USA

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Matthew D Ringel Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA

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& Shah 2014 ). Unfortunately, these treatments only delay disease progression and/or induce transient partial remissions, highlighting the importance of new research in this area. Genetic alterations that result in enhanced activation of the MAPK and

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