Hereditary diffuse gastric cancer spectrum associated with germline <i>CTNNA1</i> loss of function revealed by clinical and molecular data from 351 carrier families and over 37 000 non-carrier controls
We provide compelling evidence supporting that <i>CTNNA1</i>-truncating variants positively associate with DGC and LBC, and NMD as the pathophysiological mechanism leading to <i>CTNNA1</i> downregulation. We demonstrate that compared with <i>CDH1</i>, <i>CTNNA1</i> is a moderate penetrance HDGC gene. This new knowledge is essential to define surveillance and/or prophylactic measures for <i>CTNNA1</i>-carrier individuals and families.
Authors
- Ana Patiño‐García (ORCID: https://orcid.org/0000-0002-4066-8203)
- Lise Boussemart (ORCID: https://orcid.org/0000-0003-0935-3358)
- Nádia Pinto (ORCID: https://orcid.org/0000-0002-1903-4206)
- Patrick R. Benusiglio (ORCID: https://orcid.org/0000-0003-1003-1997)
- Rachid Karam (ORCID: https://orcid.org/0000-0002-5645-498X)
- Annemieke Cats (ORCID: https://orcid.org/0000-0001-6509-9804)
- Sigrid Tinschert (ORCID: https://orcid.org/0000-0001-7256-2481)
- Jolanda M. van Dieren (ORCID: https://orcid.org/0000-0003-3958-4990)
- Silvana Lobo (ORCID: https://orcid.org/0000-0002-5705-2958)
- Florence Coulet (ORCID: https://orcid.org/0000-0002-5325-5272)
- Kasmintan A. Schrader (ORCID: https://orcid.org/0000-0002-7413-4314)
- Robert Hüneburg (ORCID: https://orcid.org/0000-0001-9957-8299)
- Adrià López‐Fernández (ORCID: https://orcid.org/0000-0002-2844-5998)
- Irene Gullo (ORCID: https://orcid.org/0000-0003-3377-0530)
- Sergi Castellvı́-Bel (ORCID: https://orcid.org/0000-0003-1217-5097)
- Bryson W. Katona (ORCID: https://orcid.org/0000-0001-8186-9119)
- Daniela de Oliveira (ORCID: https://orcid.org/0000-0002-6636-7556)
- Chrystelle Colas (ORCID: https://orcid.org/0000-0001-9146-9346)
- Vivian E. Strong (ORCID: https://orcid.org/0000-0001-5044-1662)
- Augusto Perazzolo Antoniazzi (ORCID: https://orcid.org/0000-0003-4766-6806)
- Carolyn Horton (ORCID: https://orcid.org/0000-0001-5186-6208)
- Isabel Spier (ORCID: https://orcid.org/0000-0003-2407-7427)
- Manuel R. Teixeira (ORCID: https://orcid.org/0000-0002-4896-5982)
- Leticia Moreira (ORCID: https://orcid.org/0000-0002-4518-8591)
- Marta Vaz Batista (ORCID: https://orcid.org/0000-0001-5791-2092)
- Jacob Nattermann (ORCID: https://orcid.org/0000-0001-5972-0780)
- Monika Laszkowska (ORCID: https://orcid.org/0000-0001-6816-3293)
- Manuel Almeida (ORCID: https://orcid.org/0000-0003-2179-4738)
- Carla Oliveíra (ORCID: https://orcid.org/0000-0001-8340-2264)
- Pierre Bourgoin (ORCID: https://orcid.org/0000-0001-7713-8153)
- Paul J Gundlach
- Edenir Inêz Palmero (ORCID: https://orcid.org/0000-0003-1904-2158)
- Jeremy L. Davis (ORCID: https://orcid.org/0000-0002-6334-6936)
- Conxi Lázaro (ORCID: https://orcid.org/0000-0002-7198-5906)
- Verena Steinke‐Lange (ORCID: https://orcid.org/0000-0001-8491-3234)
- Melyssa Aronson (ORCID: https://orcid.org/0000-0002-7503-5799)
- Celina São José (ORCID: https://orcid.org/0000-0003-4292-3957)
- Judith Balmañà (ORCID: https://orcid.org/0000-0002-0762-6415)
- Augusto Q. Pedro (ORCID: https://orcid.org/0000-0001-8194-6022)
- Joana Guerra (ORCID: https://orcid.org/0000-0001-5259-1453)
- Alexandre Dias (ORCID: https://orcid.org/0000-0002-5110-5764)
- Liselotte P. van Hest (ORCID: https://orcid.org/0000-0002-9373-6601)
- Hélène Delhomelle
- Jennifer Herrera-Mullar (ORCID: https://orcid.org/0009-0001-7861-178X)
- Paulo S. Pereira
- Sérgio B. Sousa (ORCID: https://orcid.org/0000-0003-3921-1334)
- Lisa Golmard
- Magali Svrcek
- Sergio Carrera
- Lizet E. van der Kolk
- Paul Mansfield
- Stefan Aretz
- Marta Ferreira
- Dana Clark (ORCID: https://orcid.org/0000-0001-8052-0118)
- Birthe Zäncker
- André Pinto-Oliveira
Institutions
- Hebron University (PS)
- Universitat Autònoma de Barcelona (ES)
- BC Cancer Agency (CA)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Bonn (DE)
- Innsbruck Medical University (AT)
- Inserm (FR)
- Universidade do Porto (PT)
- Universität Innsbruck (AT)
- Cornell University (US)
- University Hospital Bonn (DE)
- The Netherlands Cancer Institute (NL)
- Hospital de São João (PT)
- LMU Klinikum (DE)
- Sorbonne Université (FR)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Hospital de Câncer de Barretos (BR)
- Departament de Salut (ES)
- Hôpital Saint-Antoine (FR)
- Instituto Português de Oncologia Francisco Gentil (PT)
- Institut Català d'Oncologia (ES)
- Administração Regional de Saúde de Lisboa e Vale do Tejo (PT)
- National Center for Tumor Diseases (DE)
- Navarre Institute of Health Research (ES)
- Institute of Human Genetics (PL)
- Pitié-Salpêtrière Hospital (FR)
- Cancer Genomics Centre (NL)
- Vall d'Hebron Hospital Universitari (ES)
- Sinai Health System (CA)
- Paris Cardiovascular Research Center (FR)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- Centre de Recherche Saint-Antoine (FR)
- Hospital de Cruces (ES)
- Hospital Braga (PT)
- National Cancer Institute (US)
- Instituto Nacional de Câncer - INCA (BR)
- Center for Cancer Research (US)
- Erasmus MC Cancer Institute (NL)
- Ambry Genetics (United States) (US)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto (PT)
- Institute of Biomedical Science (GB)
- Unidade Hospitalar de Bragança (PT)
- University Hospital Carl Gustav Carus (DE)
- Klinik und Poliklinik für Psychotherapie und Psychosomatik (DE)
- Universitat de Barcelona (ES)
- University of Coimbra (PT)
- University of Pennsylvania (US)
- Institut Curie (FR)
- Universidad de Navarra (ES)
- Nantes Université (FR)
Publication Details
- Journal
- Gut
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1136/gutjnl-2024-334601
- Citations
- 4
- Primary Topic
- Genetic factors in colorectal cancer
- Type
- article
- Field-Weighted Citation Impact
- 5.89
Funders
- Fundación Cellex
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Ministério da Ciência, Tecnologia e Inovação
- Ministério da Saúde
- Universidade do Porto
- National Institutes of Health
- HORIZON EUROPE Framework Programme
- European Regional Development Fund
- Agencia Estatal de Investigación
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases