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Case Reports Journal Article Ppublish 10 citations

PubMed: 33454955 DOI: 10.1111/cge.13925

Further delineation of the NTHL1 associated syndrome: A report from the French Oncogenetic Consortium.

Clin Genet 99(5):662-672

Authors: Flavie Boulouard, Edwige Kasper, Marie-Pierre Buisine, Gwendoline Lienard, Stéphanie Vasseur, Sandrine Manase, Michel Bahuau, Emmanuelle Barouk Simonet, Virginie Bubien, Florence Coulet, Véronica Cusin, Marion Dhooge, Lisa Golmard, Vincent Goussot, Nadim Hamzaoui, Elodie Lacaze, Sophie Lejeune, Jacques Mauillon, Marie-Pascale Beaumont, Stéphane Pinson, Camille Tlemsani, Christine Toulas, Jean-Marc Rey, Nancy Uhrhammer, Gaëlle Bougeard, Thierry Frebourg, Claude Houdayer, Stéphanie Baert-Desurmont

Affiliations

  • Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France.
  • Comprehensive Cancer Center François Baclesse, Laboratory of Cancer Biology and Genetics, Caen, France.
  • Department of Biochemistry and Molecular Biology, Lille University Hospital Center, UMR 1277 Inserm-9020 CNRS, Lille University, Lille, France.
  • Medical genetics Department, Henri Mondor Hospital, Créteil, France.
  • Cancer Genetics Unit, Institut Bergonie, Bordeaux, France.
  • Department of Genetics, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.
  • Gastroenterology Unit, Cochin University Hospital, Paris Descartes University, Paris, France.
  • Institut Curie, Department of Genetics and Paris Sciences, Lettres Research University, Paris, France.
  • Department of Tumor Biology and Pathology, Georges-François Leclerc Center, Dijon, France.
  • Department of Oncogenetics, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France.
  • Department of Genetics, Le Havre General Hospital, Normandy Centre for Genomic and Personalized Medicine, Le Havre, France.
  • Genetic Pathology Biology Department, Lille University Hospital Center, Jeanne de Flandre Hospital, Lille, France.
  • Department of Genetics, Rennes University Hospital Center, Rennes, France.
  • Genetics Department, Hospices Civils de LYON (HCL), University Hospital, East Pathology Center, Bron, France.
  • Oncogenetic Laboratory, Cancer University Institute Toulouse Oncopole, Toulouse, France.
  • Department of Pathology and Oncobiology, Montpellier University Hospital, Montpellier, France.
  • Centre Jean Perrin, Oncogenetics and Clermont Auvergne University, INSERM U1240, Clermont-Ferrand, France.

Abstract

Biallelic pathogenic variants in the NTHL1 (Nth like DNA glycosylase 1) gene cause a recently identified autosomal recessive hereditary cancer syndrome predisposing to adenomatous polyposis and colorectal cancer. Half of biallelic carriers also display multiple colonic or extra-colonic primary tumors, mainly breast, endometrium, urothelium, and brain tumors. Published data designate NTHL1 as an important contributor to hereditary cancers but also underline the scarcity of available informations. Thanks to the French oncogenetic consortium (Groupe Génétique et Cancer), we collected NTHL1 variants from 7765 patients attending for hereditary colorectal cancer or polyposis (n = 3936) or other hereditary cancers (n = 3829). Here, we describe 10 patients with pathogenic biallelic NTHL1 germline variants, that is, the second largest NTHL1 series. All carriers were from the "colorectal cancer or polyposis" series. All nine biallelic carriers who underwent colonoscopy presented adenomatous polyps. For digestive cancers, average age at diagnosis was 56.2 and we reported colorectal, duodenal, caecal, and pancreatic cancers. Extra-digestive malignancies included sarcoma, basal cell carcinoma, breast cancer, urothelial carcinoma, and melanoma. Although tumor risks remain to be precisely defined, these novel data support NTHL1 inclusion in diagnostic panel testing. Colonic surveillance should be conducted based on MUTYH recommendations while extra-colonic surveillance has to be defined.

MeSH

Genes, Adenomatous Polyps, Neoplasms, Breast, Colorectal Neoplasms, Genetics, Medical, Colonic Neoplasms

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