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Clinical implications of CTNNA1 germline mutations in asymptomatic carriers

  • Patrick R. Benusiglio
  • Chrystelle Colas
  • Erell Guillerm
  • Axelle Canard
  • Hélène Delhomelle
  • Mathilde Warcoin
  • Jérôme Bellanger
  • Mélanie Eyries
  • Mohamed Zizi
  • Jeanne Netter
  • Florent Soubrier
  • Yann Parc
  • Anne Mourregot
  • Aurélie Maran Gonzalez
  • Veronica Cusin
  • Jérôme A. Denis
  • Isabelle Coupier
  • Magali Svrcek
  • Florence Coulet
Short Communication
  • 60 Downloads

Abstract

In 2017, we implemented CTNNA1 germline analysis in probands suspected of having hereditary diffuse gastric cancer. Here, we report the results from a retrospective series of 41 cases, including the identification of a new family with a CTNNA1 mutation and the first prophylactic total gastrectomy in an asymptomatic carrier after a normal upper endoscopy. Diffuse gastric cancer foci with loss of catenin alpha-1 expression were seen in the resected tissue, suggesting that CTNNA1 and CDH1 germline mutations behave in a similar manner. Life-changing prophylactic total gastrectomy should therefore also be considered in CTNNA1 mutation carriers.

Keywords

Diffuse gastric cancer CDH1 CTNNA1 Signet-ring cell Hereditary cancer 

Notes

Acknowledgements

We are grateful to the following colleagues whose patients were included in this study: Sylviane Olschwang, Pierre Laurent-Puig, Nadem Soufir and Emmanuelle Barouk-Simonet. We also thank Véronique Byrde for logistical assistance. The pedigree was drawn using Invitae’s Family History Tool: https://www.invitae.com/en/familyhistory/.

Author contributions

Manuscript writing: PRB, CC, MS and FC. Data collection: PRB, CC, EG, HD, MW, FC. Patient management (clinical): PRB, CC, HD, MW, JB, JN, YP, AM, VC, IC. Genetic analyses: EG, ME, MZ, FS, JD, FC. Pathology: AC, AMG, MS. Final draft approval: all authors.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

Ethical standards

Retrospective results on a case series are reported in this manuscript. All patients benefited from in-person genetic counseling by a physician with expertise in clinical cancer genetics. They then signed an informed consent form clearly stating that gastric cancer susceptibility genes would be analyzed. Work was done in accordance with French law and National guidelines edited by Health Authorities.

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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018

Authors and Affiliations

  • Patrick R. Benusiglio
    • 1
    • 2
  • Chrystelle Colas
    • 1
    • 2
    • 3
  • Erell Guillerm
    • 4
  • Axelle Canard
    • 5
  • Hélène Delhomelle
    • 2
  • Mathilde Warcoin
    • 1
  • Jérôme Bellanger
    • 2
    • 6
  • Mélanie Eyries
    • 4
  • Mohamed Zizi
    • 4
  • Jeanne Netter
    • 2
  • Florent Soubrier
    • 4
    • 7
  • Yann Parc
    • 2
    • 7
  • Anne Mourregot
    • 8
  • Aurélie Maran Gonzalez
    • 9
  • Veronica Cusin
    • 1
    • 10
  • Jérôme A. Denis
    • 4
    • 7
    • 11
  • Isabelle Coupier
    • 12
  • Magali Svrcek
    • 5
    • 7
  • Florence Coulet
    • 4
    • 7
  1. 1.Consultation d’Oncogénétique, Unité fonctionnelle d’Oncogénétique, Département de GénétiqueGroupe Hospitalier Pitié-Salpêtrière AP-HPParisFrance
  2. 2.Service de Chirurgie générale et digestiveHôpital Saint-Antoine AP-HPParisFrance
  3. 3.Service de GénétiqueInstitut CurieParisFrance
  4. 4.Laboratoire d’Oncogénétique, Unité fonctionnelle d’Oncogénétique, Département de GénétiqueGroupe Hospitalier Pitié-Salpêtrière AP-HPParisFrance
  5. 5.Service d’Anatomie et Cytologie pathologiquesHôpital Saint-Antoine AP-HPParisFrance
  6. 6.Service de Gastro-entérologie et NutritionHôpital Saint-Antoine AP-HPParisFrance
  7. 7.Sorbonne Université, Faculté de MédecineParisFrance
  8. 8.Département de Chirurgie OncologiqueInstitut du Cancer de Montpellier (ICM)MontpellierFrance
  9. 9.Service d’Anatomie PathologiqueInstitut du Cancer de Montpellier (ICM)MontpellierFrance
  10. 10.Institut de Cancérologie, Hôpital Privé des PeupliersParisFrance
  11. 11.Service de Biochimie endocrinienne et oncologiqueGroupe Hospitalier Pitié-Salpêtrière AP-HPParisFrance
  12. 12.Unité d’Oncogénétique, Service de GénétiqueCHU de MontpellierMontpellierFrance

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