Article Text

Download PDFPDF
Short report
CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study
  1. Patrick R Benusiglio1,
  2. David Malka1,
  3. Etienne Rouleau2,
  4. Antoine De Pauw3,
  5. Bruno Buecher3,
  6. Catherine Noguès2,
  7. Emmanuelle Fourme2,
  8. Chrystelle Colas4,
  9. Florence Coulet4,
  10. Mathilde Warcoin4,
  11. Sophie Grandjouan5,
  12. Alain Sezeur6,
  13. Pierre Laurent-Puig7,
  14. Diane Molière7,
  15. Camille Tlemsani1,
  16. Marina Di Maria1,
  17. Veronique Byrde1,
  18. Suzette Delaloge1,
  19. Martine Blayau8,
  20. Olivier Caron1
  1. 1Consultation d'Oncogénétique, Département de Médecine Oncologique, Institut Gustave Roussy, Villejuif, France
  2. 2Consultation et Laboratoire d'Oncogénétique, Hôpital René Huguenin, Saint-Cloud, France
  3. 3Service de Génétique Oncologique, Institut Curie, Paris, France
  4. 4Centre de Génétique Moléculaire et Chromosomique, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France
  5. 5Consultation d'Oncogénétique, Centre Hospitalier Universitaire Cochin, Paris, France
  6. 6Service de chirurgie digestive, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France
  7. 7Consultation d'Oncogénétique, Hôpital Européen Georges Pompidou, Paris, France
  8. 8Service de Génétique Moléculaire et Génomique, Centre Hospitalier Universitaire de Rennes, Rennes, France
  1. Correspondence to Patrick R Benusiglio, Consultation d'Oncogénétique, Département de Médecine Oncologique, Institut Gustave Roussy, 114 rue Edouard Vaillant, Villejuif 94805, France; pbenusiglio.wk{at}


Introduction CDH1 predisposes primarily to diffuse gastric cancer (DGC). Multiple DGC cases in a family, DGC at a young age in an individual or the combination of DGC andlobular breast cancer (LBC) in an individual or a family define the hereditary DGC syndrome (HDGC), and testing for germline CDH1 mutations is warranted in HDGC.

Methods and results We report all index cases from Ile-de-France in which a germline CDH1 mutation has been identified. Out of 18 cases, 7 do not fulfil the HDGC-defining criteria. Three of them are women who presented initially with bilateral LBC below age 50, without personal or family history of DGC, and who subsequently developed symptomatic DGC.

Discussion Our series of CDH1 mutation carriers is the largest to date and demonstrates that LBC might be the first manifestation of HDGC. A personal or family history of multiple LBCs at a young age, even without DGC, should prompt CDH1 mutation screening. It is paramount to identify mutation carriers early, so that they can benefit from prophylactic gastrectomy before they develop symptomatic, highly lethal DGC. We recommend a revision of the HDGC-defining criteria and propose for consideration the name ‘Hereditary Diffuse Gastric and Lobular Breast Cancer’ instead of HDGC.

  • Cancer: gastric
  • Cancer: breast
  • Clinical genetics
  • Oncology
  • Prevention

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.