Clinical implications of CTNNA1 germline mutations in asymptomatic carriers
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.
KeywordsDiffuse gastric cancer CDH1 CTNNA1 Signet-ring cell Hereditary cancer
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/.
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.
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.