1. Hereditary diffuse gastric cancer syndrome: improved performances of the 2015 testing criteria for the identification of probands with aCDH1germline mutation
- Author
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Olivier Caron, David Malka, Audrey Remenieras, Bruno Buecher, Patrick R. Benusiglio, Camille Tlemsani, Mathilde Warcoin, Dominique Stoppa-Lyonnet, Qing Wang, Chystelle Colas, Jessica Moretta, Emmanuelle Mouret-Fourme, Pierre Romero, Martine Blayau, Sophie Grandjouan, Etienne Rouleau, Marina Di Maria, Nancy Uhrhammer, Antoine De Pauw, Catherine Noguès, Institut National du Cancer [Boulogne Billancourt] (INC), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Curie [Paris], Département d'Oncogénétique, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Laboratoire de diagnostic génétique et moléculaire, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Service de Génétique Oncologique, Institut Gustave Roussy (IGR), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique clinique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Institut National du Cancer [Boulogne Billancourt] ( INC ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut Curie, CRLCC Jean Perrin, Centre Jean Perrin, INSTITUT CURIE, Institut Gustave Roussy ( IGR ), CHU Cochin [AP-HP], Université de Rennes 1 ( UR1 ), and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud
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Oncology ,Proband ,medicine.medical_specialty ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Sensitivity and Specificity ,Germline ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,Breast cancer screening ,Germline mutation ,Breast cancer ,Antigens, CD ,Stomach Neoplasms ,Internal medicine ,Genetics ,medicine ,Humans ,Genetic Testing ,[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics ,Germ-Line Mutation ,Genetics (clinical) ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Cancer ,Cadherins ,medicine.disease ,3. Good health ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Immunology ,Medical genetics ,Hereditary diffuse gastric cancer ,business - Abstract
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 …
- Published
- 2015
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