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Hereditary diffuse gastric cancer syndrome: improved performances of the 2015 testing criteria for the identification of probands with a CDH1 germline mutation
  1. Patrick R Benusiglio1,
  2. Chystelle Colas2,
  3. Etienne Rouleau3,
  4. Nancy Uhrhammer4,
  5. Pierre Romero4,
  6. Audrey Remenieras5,
  7. Jessica Moretta6,
  8. Qing Wang7,
  9. Antoine De Pauw3,
  10. Bruno Buecher3,
  11. Dominique Stoppa-Lyonnet3,8,
  12. Emmanuelle Mouret-Fourme3,
  13. Catherine Noguès3,
  14. Marina Di Maria1,
  15. Camille Tlemsani9,
  16. Mathilde Warcoin2,
  17. Sophie Grandjouan10,
  18. David Malka1,
  19. Olivier Caron1,
  20. Martine Blayau11
  1. 1Consultation d'Oncogénétique, Département de Médecine Oncologique, Gustave Roussy Cancer Campus, Villejuif, France
  2. 2Centre de Génétique Moléculaire et Chromosomique, Centre Hospitalier Universitaire Pitié-Salpêtrière AP-HP, Paris, France
  3. 3Consultation et Laboratoire d'Oncogénétique, Institut Curie, Paris et Saint-Cloud, Paris, France
  4. 4Laboratoire de Diagnostic Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France
  5. 5Oncogénétique Moléculaire, CLCC Institut Paoli-Calmettes, Marseille, France
  6. 6Département d'Anticipation et de Suivi du Cancer, CLCC Institut Paoli-Calmettes, Marseille, France
  7. 7Plateforme de Génétique Constitutionnelle, Centre Léon Bérard, Lyon, France
  8. 8Université Paris-Descartes, Sorbonne Paris Cité, Paris, France
  9. 9Service d'Oncologie, Centre Hospitalier Universitaire Cochin AP-HP, Paris, France
  10. 10Consultation d'Oncogénétique, Centre Hospitalier Universitaire Cochin AP-HP, Paris, France
  11. 11Service de Génétique Moléculaire et Génomique, Centre Hospitalier Universitaire de Rennes, Rennes, France
  1. Correspondence to Dr Patrick R Benusiglio, Département de Médecine Oncologique, Gustave Roussy Cancer Campus, Villejuif 94805, France; pbenusiglio.wk{at}

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The international, consensus testing criteria for CDH1 germline mutations were recently revised in order to increase their performances, particularly their sensitivity. It is paramount to identify a high proportion of actual mutation carriers, as finding a mutation in a proband and subsequently in some of his relatives allows for risk-reducing recommendations regarding diffuse gastric cancer (DGC) and lobular breast cancer (LBC). We collected data on all French probands tested for CDH1 in a retrospective study on the hereditary DGC syndrome (HDGC). Out of 627 probands, 52 were carriers. We compared the new, 2015 version of these criteria to the 2010 version, and showed that both the sensitivity and the Youden index (J), an index that estimates the criteria discriminating power, increased.

CDH1 is a tumour suppressor gene located on chromosome 16q22. It codes for the E-cadherin adhesion protein. Monoallelic germline mutations in CDH1 cause HDGC, in which carriers have a high lifetime risk of DGC (also called signet ring cell gastric cancer), and LBC (reviewed in ref. 1). In clinical practice, mutations are first identified in a proband with a personal history of DGC and/or LBC, and adult relatives are subsequently tested to see whether they also carry the mutation. Asymptomatic carriers are then advised to undergo risk-reducing gastrectomy, and for women annual breast cancer screening using MRI. The International Gastric Cancer Linkage Consortium defined clinical criteria warranting CDH1 germline testing in a proband. The criteria were first published in 1999 and then updated in 2010.2 ,3 A new 2015 version is being published in this issue of the Journal of Medical Genetics …

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  • Contributors Design of the study: PRB, ER, OC and MB. Genetic counselling and clinical management of patients: PRB, CC, JM, ADP, BB, DS-L, EM-F, CN, MDM, MW, SG, DM and OC. Gene analysis: CC, ER, NU, AR, QW and MB. Data collection: PRB, CC, ER, NU, PR, AR, QW, ADP, CT, MW and MB. Data analysis and interpretation: PRB and EMF. Drafting of the manuscript: PRB. Critical review and approval of the manuscript: all authors. Guarantor: PRB.

  • Competing interests None declared.

  • Ethics approval Gene analysis was prescribed by cancer geneticists within accredited, institution-approved, cancer genetics clinics. All participating laboratories were accredited by the French National Cancer Institute.

  • Provenance and peer review Not commissioned; externally peer reviewed.