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Jairo Arturo Pinzón-Cortés Biological Sciences Department, Laboratory of Human Genetics, Universidad de los Andes, Bogotá, Colombia
School of Medicine, Universidad de los Andes, Bogotá, Colombia

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Angelina Perna-Chaux Biological Sciences Department, Laboratory of Human Genetics, Universidad de los Andes, Bogotá, Colombia

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Nicolás Steven Rojas-Villamizar Biological Sciences Department, Laboratory of Human Genetics, Universidad de los Andes, Bogotá, Colombia

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Angélica Díaz-Basabe Biological Sciences Department, Laboratory of Human Genetics, Universidad de los Andes, Bogotá, Colombia

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Diana Carolina Polanía-Villanueva Biological Sciences Department, Laboratory of Human Genetics, Universidad de los Andes, Bogotá, Colombia

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María Fernanda Jácome Biological Sciences Department, Laboratory of Human Genetics, Universidad de los Andes, Bogotá, Colombia

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Carlos Olimpo Mendivil School of Medicine, Universidad de los Andes, Bogotá, Colombia
Endocrinology Section, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia

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Helena Groot Biological Sciences Department, Laboratory of Human Genetics, Universidad de los Andes, Bogotá, Colombia
School of Medicine, Universidad de los Andes, Bogotá, Colombia

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Valeriano López-Segura Biological Sciences Department, Laboratory of Human Genetics, Universidad de los Andes, Bogotá, Colombia
School of Medicine, Universidad de los Andes, Bogotá, Colombia

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methylation and demethylation processes in diabetes may be differently affected depending on the local conditions and tissue exposed to the disease ( 17 ). Concerning the source of the observed differences in DNA methylation, they can be attributed to

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A H Ludwig-Slomczynska Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland

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S Borys Department of Metabolic Diseases, Jagiellonian University Medical College
University Hospital, Krakow, Poland

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M T Seweryn Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland

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J Hohendorff Department of Metabolic Diseases, Jagiellonian University Medical College
University Hospital, Krakow, Poland

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P Kapusta Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland

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B Kiec-Wilk Department of Metabolic Diseases, Jagiellonian University Medical College
University Hospital, Krakow, Poland

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E Pitera Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland

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P P Wolkow Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland

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M T Malecki Department of Metabolic Diseases, Jagiellonian University Medical College
University Hospital, Krakow, Poland

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- and post-treatment). Bisulfite conversion was performed using 500 ng of DNA with EZ DNA Methylation-Direct Kit (Zymo, Irvine, CA, USA). The next steps were performed according to the Illumina protocol of Methylation EPIC kit (Illumina, San Diego, CA

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Ya-Fen Hu Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
Department of Endocrinology, The People’s Hospital of Daxing District, Beijing, China

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Lin Hua Department of Mathematics, School of Biomedical Engineering, Capital Medical University, Beijing, China

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Xiu Tuo Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Ting-Ting Shi Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Yi-Lin Yang Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Yun-Fu Liu Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Zhong-Yu Yan Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Zhong Xin Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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outer edge of the orbit was at the lowest point. Identification of candidate genes In a previous study, a genome-scale screening of DNA methylation was performed on the peripheral blood sample from six patients with GO and six controls

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Jessica S Jarmasz Department of Physiology & Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

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Yan Jin Department of Physiology & Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

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Hana Vakili Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

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Peter A Cattini Department of Physiology & Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

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chromatin that influence gene expression ( 23 ). The methylation of cytosine paired with a guanine (CpG) termed ‘DNA methylation’ is one of the many epigenetic mechanisms that govern gene expression where appro­ximately 70–80% of CpG dinucleotides are

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Kristian Almstrup Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Hanne Frederiksen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anna-Maria Andersson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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epigenetic studies. We have previously published one of the first studies demonstrating changes in DNA methylation patterns with the onset of puberty in healthy children ( 12 ) and identified the promotor of the thyroid hormone receptor interactor 6 gene

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Elham Barazeghi Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden

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Per Hellman Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden

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Gunnar Westin Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden

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Peter Stålberg Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden

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tumors ( 4 ). Promoter DNA methylation studies revealed increased RASSF1A / CTNNB1 methylation associated with metastatic progression, and epigenetic repression of TCEB3C in SI-NETs ( 5 , 6 ). A comprehensive integrated molecular analysis of a large

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Anne Jouinot Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
Department of Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Juliane Lippert Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany

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Martin Fassnacht Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany
Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany

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Bruno de La Villeon Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France

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Amandine Septier Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France

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Mario Neou Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France

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Karine Perlemoine Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France

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Silke Appenzeller Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany

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Mathilde Sibony Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
Department of Pathology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Sébastien Gaujoux Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
Department of Digestive and Endocrine Surgery, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Bertrand Dousset Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
Department of Digestive and Endocrine Surgery, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Rossella Libe Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
Department of Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Lionel Groussin Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
Department of Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Cristina L Ronchi Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany
Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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Guillaume Assié Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
Department of Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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Jérôme Bertherat Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
Department of Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France

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mutations, chromosome alteration and DNA methylation profile, or at the RNA level, including transcriptome and targeted gene expression profiles. Intratumor heterogeneity of somatic mutations has been reported in many cancer types ( 12 , 13 , 14 ). In a

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Roberto Cosimo Melcangi Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy

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Livio Casarini Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy

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Marco Marino Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy

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Daniele Santi Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy

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Samantha Sperduti Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy

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Silvia Giatti Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy

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Silvia Diviccaro Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy

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Maria Grimoldi Neurology Division, Papa Giovanni XXIII Hospital, Bergamo, Italy

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Donatella Caruso Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy

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Guido Cavaletti Experimental Neurology Unit and Milan Center for Neuroscience, School of Medicine and Surgery, University of Milano Bicocca, Monza, Italy

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Manuela Simoni Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy
Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy

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analysed in duplicate and the percentage of DNA methylation was calculated using the previously described 2 −ΔΔCt method ( 35 ) optimised for DNA methylation analyses ( 36 , 37 ). Briefly, ΔCt values were calculated by subtracting the internal control Ct

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Hui Li Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, P. R. China.

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Peng Wu Department of Thyroid Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, P. R. China.

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various diseases, including thyroid cancer ( 3 , 4 ). This regulation includes DNA methylation, chromatin remodeling, histone modifications, and the expression of diverse non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and

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Helene Bandsholm Leere Tallaksen Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

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Emma B Johannsen Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

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Jesper Just Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

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Mette Hansen Viuff Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Gynaecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark

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Claus H Gravholt Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark

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Anne Skakkebæk Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark

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chromosome abnormalities,’ ‘Turner syndrome,’ ‘Klinefelter syndrome,’ ‘47,XYY,’ and ‘47,XXX’ as search terms in combination with ‘DNA methylation,’ ‘transcriptome profile,’ ‘epigenetics,’ and ‘genomics’. Relevant articles were obtained and reviewed as well as

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