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Tanya K Day
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Tina Bianco-Miotto Dame Roma Mitchell Cancer Research Laboratories, School of Paediatrics and Reproductive Health, School of Agriculture, Discipline of Medicine, Hanson Institute, Adelaide Prostate Cancer Research Centre, The University of Adelaide, Adelaide, South Australia, Australia
Dame Roma Mitchell Cancer Research Laboratories, School of Paediatrics and Reproductive Health, School of Agriculture, Discipline of Medicine, Hanson Institute, Adelaide Prostate Cancer Research Centre, The University of Adelaide, Adelaide, South Australia, Australia

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excellent therapeutic targets. Epigenetic modifications like DNA methylation are also stable and technically easy to assess making them ideal biomarkers for diagnosis and prognosis. It is well established from candidate gene studies that epigenetic

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Peng Hou Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA

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Dingxie Liu Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA

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Mingzhao Xing Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA

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, 2007 a ). The specific molecular mechanisms underlying PTC tumorigenesis driven by the BRAF mutation have not been well understood. This is particularly the case in epigenetic aspects. For example, the role of aberrant gene methylation and its extent

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Takaya Kodama Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Kenji Oki Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Yu Otagaki Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Ryuta Baba Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Akira Okada Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Kiyotaka Itcho Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Kazuhiro Kobuke Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Gaku Nagano Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Haruya Ohno Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Nobuyuki Hinata Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Koji Arihiro Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan

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Celso E Gomez-Sanchez Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, Mississippi, USA
Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, USA

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Masayasu Yoneda Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Noboru Hattori Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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CTNNB1 mutations is associated with tumorigenesis ( Goh et al. 2014 , Baba et al. 2021 ). Gene transcription is regulated by transcription factors and epigenetic changes in the gene. DNA methylation involves the transfer of a methyl group onto

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Carles Zafon Diabetes and Metabolism Research Unit (VHIR) and Department of Endocrinology, University Hospital Vall d’Hebron and Autonomous University of Barcelona, Barcelona, Spain
Consortium for the Study of Thyroid Cancer (CECaT), Catalonia, Spain

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Joan Gil Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Barcelona, Spain

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Beatriz Pérez-González Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Barcelona, Spain

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Mireia Jordà Consortium for the Study of Thyroid Cancer (CECaT), Catalonia, Spain
Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Barcelona, Spain

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some CpG-rich regions called CpG islands (CGIs), which are often unmethylated and encompass the promoters of approximately 60% of protein-coding genes ( Ehrlich et al. 1982 , Bird 1986 , Lister et al. 2009 ). DNA methylation is frequently

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Laura M S Seeber
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Ronald P Zweemer
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Luigi Marchionni Department of Gynaecological Oncology, Department of Oncology, Department of Obstetrics and Gynaecology (791), Department of Pathology, Department of Gynaecological Oncology, Department of Pathology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands

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Leon F A G Massuger Department of Gynaecological Oncology, Department of Oncology, Department of Obstetrics and Gynaecology (791), Department of Pathology, Department of Gynaecological Oncology, Department of Pathology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands

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Vincent T H B M Smit Department of Gynaecological Oncology, Department of Oncology, Department of Obstetrics and Gynaecology (791), Department of Pathology, Department of Gynaecological Oncology, Department of Pathology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands

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W Marchien van Baal Department of Gynaecological Oncology, Department of Oncology, Department of Obstetrics and Gynaecology (791), Department of Pathology, Department of Gynaecological Oncology, Department of Pathology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands

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René H M Verheijen
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Paul J van Diest Department of Gynaecological Oncology, Department of Oncology, Department of Obstetrics and Gynaecology (791), Department of Pathology, Department of Gynaecological Oncology, Department of Pathology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands

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the genome, methylation of CpG islands occurs ( Baylin & Herman 2000 ). These CpG islands are cytosine- and guanine-rich areas in the promoter regions of genes that are involved in cell cycle, cell adherence, DNA repair and apoptosis. Methylation of

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A Rody
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U Holtrich
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C Solbach
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K Kourtis
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G von Minckwitz
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K Engels
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S Kissler
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R Gätje
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T Karn
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M Kaufmann
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Introduction DNA methylation is a ubiquitous process of gene inactivation in nature (reviewed in Bird 2002 ). It occurs preferentially at CpG dinucleotides. In normal cells, most of the 5-methyl-cytosine is found to be associated

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Ana Carolina Bueno Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Rui M P da Silva Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Mônica F Stecchini Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Junier Marrero-Gutiérrez Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Danillo C de Almeida e Silva Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
Department of Computation and Mathematics, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Izilda Cardinalli Boldrini Children’s Center, State University of Campinas, Campinas, Sao Paulo, Brazil

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Carlos Alberto Scrideli Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Thais Junqueira Boldrini Children’s Center, State University of Campinas, Campinas, Sao Paulo, Brazil

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Carlos A F Molina Department of Surgery and Anatomy Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Fernando Silva Ramalho Department of Pathology Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Silvio Tucci Jr Department of Surgery and Anatomy Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Fernanda Borchers Coeli-Lacchini Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Ayrton Custodio Moreira Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Leandra N Z Ramalho Department of Pathology Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Silvia Brandalise Boldrini Children’s Center, State University of Campinas, Campinas, Sao Paulo, Brazil

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José Andres Yunes Boldrini Children’s Center, State University of Campinas, Campinas, Sao Paulo, Brazil

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Margaret de Castro Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Ricardo Zorzetto Nicoliello Vêncio Department of Computation and Mathematics, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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Sonir R R Antonini Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

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from data normalization is shown in Supplementary Fig. 1. Candidate gene validation The methylation effect on mRNA levels was evaluated by quantitative real-time PCR, as previously described ( Bueno et al. 2022 ). The TaqMan assays (Applied

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De-tao Yin Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China
Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China

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Wenxun Wu Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China

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Mingchuang Li Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China
Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China

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Qi-en Wang Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China

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Hongqiang Li Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China
Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China

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Yongfei Wang Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China
Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China

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Yifeng Tang Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China
Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China

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Mingzhao Xing Department of Thyroid Surgery, Key Discipline Laboratory of Clinical Medicine Henan, Department of Endocrinology, Division of Radiobiology, Division of Endocrinology and Metabolism, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China

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regions of tumor suppressor genes (TSGs) is commonly observed in various cancers, including thyroid cancer ( Xing 2007 ). DNA methylation is a common epigenetic event observed in mammalian genomes, and it often mediates transcriptional repression ( Aleqria

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Cuong V Duong
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Richard D Emes Institute of Science and Technology in Medicine, School of Veterinary Medicine and Science, Keele University School of Medicine, Stoke‐on‐Trent, Staffordshire ST4 7QB. UK

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Frank Wessely Institute of Science and Technology in Medicine, School of Veterinary Medicine and Science, Keele University School of Medicine, Stoke‐on‐Trent, Staffordshire ST4 7QB. UK

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Kiren Yacqub-Usman
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Richard N Clayton
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William E Farrell
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tumours, multiple studies have described epigenetic change within gene-associated CpG islands and/or those that lead to modification of histone tails ( Ezzat 2008 , Yacqub-Usman et al . 2012 b ). In these cases, inappropriate methylation of CpG islands

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Marijn A Vermeulen Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

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Carolien H M van Deurzen Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands
BOOG Study Center/Dutch Breast Cancer Research Group, Amsterdam, The Netherlands

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Shusma C Doebar Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands

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Wendy W J de Leng Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

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John W M Martens BOOG Study Center/Dutch Breast Cancer Research Group, Amsterdam, The Netherlands
Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands

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Paul J van Diest Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

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Cathy B Moelans Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

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rearrangements. DNA methylation is a process in which DNA methyltransferase enzymes (DNMTs) add a methyl group to the 5′-carbon of cytosine in the context of cytosine guanine dinucleotides (CpG sites), a process which is associated with gene silencing, thereby

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