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J Cros Department of Pathology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France
U1149 – University Paris Diderot, Paris, France

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O Hentic Department of Gastroenterology and Pancreatology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France

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V Rebours U1149 – University Paris Diderot, Paris, France
Department of Gastroenterology and Pancreatology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France

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M Zappa Department of Radiology, AP-HP, DHU UNITY, Beaujon Hospital, Clichy, France

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N Gille Department of Pathology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France

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N Theou-Anton Department of Somatic Genetic, AP-HP, DHU UNITY, Bichat University Hospital, Paris, France

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D Vernerey Methodology and Quality of Life in Oncology Unit (EA 3181), University Hospital of Besançon, Besançon, France

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F Maire Department of Gastroenterology and Pancreatology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France

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P Lévy U1149 – University Paris Diderot, Paris, France
Department of Gastroenterology and Pancreatology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France

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P Bedossa Department of Pathology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France
U1149 – University Paris Diderot, Paris, France

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V Paradis Department of Pathology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France
U1149 – University Paris Diderot, Paris, France

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P Hammel U1149 – University Paris Diderot, Paris, France
Department of Digestive Oncology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France

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P Ruszniewski U1149 – University Paris Diderot, Paris, France
Department of Gastroenterology and Pancreatology, AP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France

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A Couvelard U1149 – University Paris Diderot, Paris, France
Department of Pathology, AP-HP, DHU UNITY, Bichat University Hospital, Paris, France

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O 6 -methylguanine-DNA methyltransferase (MGMT) function before TEM-based treatment ( Zhang et al. 2011 ). This suicide enzyme removes alkyl group from the O 6 position on guanine bases, one of the main sites of TEM-induced DNA damage. Without

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M Cives Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute

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M Ghayouri Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute

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B Morse Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute

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M Brelsford Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute

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M Black Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute

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A Rizzo Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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A Meeker Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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J Strosberg Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute

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tumor cell death. The suicide enzyme O 6 -methylguanine DNA methyltransferase (MGMT) repairs DNA by removing the O 6 -alkylguanine adducts. High levels of MGMT expression contribute to chemoresistance by counteracting the therapeutic effect of alkylating

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Louis de Mestier Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital (APHP), and Université de Paris, Clichy, France
Centre of Research on Inflammation, INSERM U1149, Paris, France

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Anne Couvelard Centre of Research on Inflammation, INSERM U1149, Paris, France
Department of Pathology, ENETS Centre of Excellence, Bichat/Beaujon University Hospitals (APHP), and Université de Paris, Clichy/Paris, France

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Anela Blazevic Division Endocrinology, Department of Internal Medicine, ENETS Centre of Excellence, Erasmus Medical Center, Rotterdam, The Netherlands

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Olivia Hentic Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital (APHP), and Université de Paris, Clichy, France

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Wouter W de Herder Division Endocrinology, Department of Internal Medicine, ENETS Centre of Excellence, Erasmus Medical Center, Rotterdam, The Netherlands

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Vinciane Rebours Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital (APHP), and Université de Paris, Clichy, France
Centre of Research on Inflammation, INSERM U1149, Paris, France

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Valérie Paradis Centre of Research on Inflammation, INSERM U1149, Paris, France
Department of Pathology, ENETS Centre of Excellence, Bichat/Beaujon University Hospitals (APHP), and Université de Paris, Clichy/Paris, France

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Philippe Ruszniewski Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital (APHP), and Université de Paris, Clichy, France
Centre of Research on Inflammation, INSERM U1149, Paris, France

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Leo J Hofland Division Endocrinology, Department of Internal Medicine, ENETS Centre of Excellence, Erasmus Medical Center, Rotterdam, The Netherlands

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Jérôme Cros Centre of Research on Inflammation, INSERM U1149, Paris, France
Department of Pathology, ENETS Centre of Excellence, Bichat/Beaujon University Hospitals (APHP), and Université de Paris, Clichy/Paris, France

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validated for clinical practice. Over the last decade, an increasing number of publications have explored whether the tumor expression of O 6 -methylguanine-DNA methyltransferase (MGMT) could influence the efficacy of alkylating agents ( Koumarianou et al

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Ophélie De Rycke Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital, Clichy, France
Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France

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Thomas Walter Department of Gastro-enterology and oncology, Hospices Civils de Lyon, Edouard Herriot University Hospital, Lyon, France

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Marine Perrier Department of Hepato-Gastroenterology and Digestive Oncology, Robert Debré University Hospital, Reims, France

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Olivia Hentic Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital, Clichy, France

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Catherine Lombard-Bohas Department of Gastro-enterology and oncology, Hospices Civils de Lyon, Edouard Herriot University Hospital, Lyon, France

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Romain Coriat Department of Gastroenterology, Cochin University Hospital, Paris, France

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Guillaume Cadiot Department of Hepato-Gastroenterology and Digestive Oncology, Robert Debré University Hospital, Reims, France

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Anne Couvelard Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France
Department of Pathology, ENETS Centre of Excellence, Bichat/Beaujon University Hospital, Paris/Clichy, France

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Philippe Ruszniewski Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital, Clichy, France
Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France

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Jérôme Cros Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France
Department of Pathology, ENETS Centre of Excellence, Bichat/Beaujon University Hospital, Paris/Clichy, France

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Louis de Mestier Department of Gastroenterology and Pancreatology, ENETS Centre of Excellence, Beaujon University Hospital, Clichy, France
Université de Paris, Centre de Recherche sur l’Inflammation, INSERM, Paris, France

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O-6-methylguanine-methyltransferase (MGMT) enzyme ( Koumarianou et al. 2015 , de Mestier et al. 2020 b ). In PanNET, high expression of MGMT seems to be associated with a lower response and shorter PFS under ALK ( Walter et al. 2015 , Cros

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Ben C Whitelaw Department of Endocrinology, King’s College Hospital NHS Foundation Trust, London, UK

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methyltransferase (MGMT) acts as a repair mechanism to remove the methyl group from guanine bases and to therefore counteract the effects of temozolomide. MGMT is sometimes referred to as a suicide enzyme because in the process of removing the methyl group, the

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Luis V Syro Department of Neurosurgery, Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia

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Fabio Rotondo Division of Pathology, Department of Laboratory Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada

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Leon D Ortiz Division of Neuro-Oncology, Instituto de Cancerologia, Clinica Las Americas. Medellin, Colombia

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Kalman Kovacs Division of Pathology, Department of Laboratory Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada

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-repair events leads to apoptosis ( Sabharwal & Middleton 2006 ). The action of TMZ depends on its accumulation in the tumor and the capacity for O 6 -methylguanine-DNA methyltransferase (MGMT), present in the cells, to repair its effects ( Kaina et al . 2007

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I Marinoni Institute of Pathology, University of Bern, Bern, Switzerland

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A Wiederkeher Institute of Pathology, University of Bern, Bern, Switzerland

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T Wiedmer Institute of Pathology, University of Bern, Bern, Switzerland
GCB Graduate School Bern, Bern, Switzerland

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S Pantasis Institute of Pathology, University of Bern, Bern, Switzerland

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A Di Domenico Institute of Pathology, University of Bern, Bern, Switzerland
GCB Graduate School Bern, Bern, Switzerland

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R Frank Institute of Pathology, University of Bern, Bern, Switzerland

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E Vassella Institute of Pathology, University of Bern, Bern, Switzerland

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A Schmitt Institute of Pathology, University of Bern, Bern, Switzerland

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A Perren Institute of Pathology, University of Bern, Bern, Switzerland

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shown in several genes ( VHL, cdkn2a (p16), RASSF1 , DAPK1 , TIMP3 , PAX5 , HIC1 , CADM1 , PYCARD , ESR1 , VHL , RARB , WT1 and MGMT ) ( House et al. 2003 , Schmitt et al. 2009 , Malpeli et al. 2011 , Schmitt et al. 2014

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Anna Koumarianou Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Stavroula Antoniou Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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George Kanakis Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Nikolaos Economopoulos Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Dimitra Rontogianni Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Anastasios Ntavatzikos Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Nikolaos Tsavaris Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Dimitrios Pectasides Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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George Dimitriadis Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Gregory Kaltsas Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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regimens may deplete O 6-methylguanine DNA methyltransferase (MGMT), an important factor in cases of TMZ resistance and/or inhibit endothelial cell proliferation and formation of tumour vasculature via the so-called metronomic effect ( Tolcher et al

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Alexa Childs Department of Oncology, Royal Free London NHS Foundation Trust, London, UK

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Amy Kirkwood Cancer Research UK & UCL Cancer Trials Centre, London, UK

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Julien Edeline UCL Cancer Institute, UCL, London, UK

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Tu Vinh Luong Department of Pathology, Royal Free London NHS Foundation Trust, London, UK

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Jennifer Watkins Department of Pathology, Royal Free London NHS Foundation Trust, London, UK

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Angela Lamarca Institute of Cancer Sciences, University of Manchester/The Christie NHS Foundation Trust, Manchester, UK

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Doraid Alrifai King’s College Hospital NHS Foundation Trust, London, UK

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Phyllis Nsiah-Sarbeng Department of Radiology, Royal Free London NHS Foundation Trust, London, UK

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Roopinder Gillmore Department of Oncology, Royal Free London NHS Foundation Trust, London, UK

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Astrid Mayer Department of Oncology, Royal Free London NHS Foundation Trust, London, UK

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Christina Thirlwell Department of Oncology, Royal Free London NHS Foundation Trust, London, UK
UCL Cancer Institute, UCL, London, UK

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Debashis Sarker King’s College Hospital NHS Foundation Trust, London, UK

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Juan W Valle Institute of Cancer Sciences, University of Manchester/The Christie NHS Foundation Trust, Manchester, UK

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Tim Meyer Department of Oncology, Royal Free London NHS Foundation Trust, London, UK
UCL Cancer Institute, UCL, London, UK

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that of Sorbye and coworkers, the majority of patients received platinum-based chemotherapy and Ki-67 may be a better predictor of response for this agent. The expression of the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) has also

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Monia Zidane INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, France
Université Paris-Sud Orsay, Île-de-France, France
Gustave Roussy, Villejuif, France

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Jean-Baptiste Cazier Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, Birmingham, UK

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Sylvie Chevillard CEA, Direction de la Recherche Fondamentale, Institut de Biologie François Jacob, iRCM, SREIT, Laboratoire de Cancérologie Expérimentale (LCE), Université Paris-Saclay, Fontenay-aux-Roses, France

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Catherine Ory CEA, Direction de la Recherche Fondamentale, Institut de Biologie François Jacob, iRCM, SREIT, Laboratoire de Cancérologie Expérimentale (LCE), Université Paris-Saclay, Fontenay-aux-Roses, France

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Martin Schlumberger Université Paris-Sud Orsay, Île-de-France, France
Gustave Roussy, Villejuif, France
UMR 8200 CNRS, Villejuif, France

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Corinne Dupuy Université Paris-Sud Orsay, Île-de-France, France
Gustave Roussy, Villejuif, France
UMR 8200 CNRS, Villejuif, France

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Jean-François Deleuze Centre National de Recherche en Génomique Humaine, CEA, Evry, France

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Anne Boland Centre National de Recherche en Génomique Humaine, CEA, Evry, France

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Nadia Haddy INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, France
Université Paris-Sud Orsay, Île-de-France, France
Gustave Roussy, Villejuif, France

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Fabienne Lesueur Institut Curie, Paris, France
PSL Research University, Paris, France
INSERM, U900, Paris, France
Mines Paris Tech, Fontainebleau, France

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Florent de Vathaire INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, France
Université Paris-Sud Orsay, Île-de-France, France
Gustave Roussy, Villejuif, France

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OGG1 Association of rs2296675 (MGMT) with DTC Individual radiation dose to the thyroid was reconstructed based on the residential history and dietary habits, and information on environmental contamination for each settlement

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