{"doi":"10.5230/jgc.2026.26.e5","title":"The Changing Landscape of Hereditary Diffuse Gastric Cancer","abstract":null,"journal":"Journal of Gastric Cancer","year":2026,"id":618279,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1594902,"name":"Kieran Redpath","orcid":"0000-0002-2221-7038","position":1,"is_corresponding":false},{"id":1594903,"name":"Emily Schulpen","orcid":"0009-0009-5514-2907","position":2,"is_corresponding":false},{"id":96284,"name":"Parry Guilford","orcid":"0000-0002-7256-9576","position":3,"is_corresponding":false},{"id":1594901,"name":"Conor Vaessen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Changing Landscape of Hereditary Diffuse Gastric Cancer","abstract":"Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome characterized by the early onset of diffuse gastric cancer (DGC) and lobular breast cancer.HDGC is predominantly caused by germline truncating mutations in CDH1, which encodes the cell-cell adhesion protein, E-cadherin.Less frequent predisposing mutations are observed in the CTNNA1 gene that encodes -catenin.E-cadherin and -catenin are components of the epithelial adherens junction and play important roles in cell adhesion, signal transduction, and cell architecture maintenance.The first step in DGC initiation in carriers of pathogenic CDH1 and CTNNA1 variants is the inactivation of wildtype CDH1 or CTNNA1 alleles, leading to the development of intramucosal gastric signet ring cell carcinomas (SRCCs).In the case of CDH1 mutations, E-cadherin loss is associated with abnormal orientation of the mitotic spindle, which is believed to result in the displacement of dividing stem or progenitor cells out of the epithelial plane and into either the glandular lumen or lamina propria.Although these early stage pT1a SRCCs are generally indolent, they can acquire aggressive traits that precede a pattern of invasive growth.HDGC is clinically managed using an increasingly balanced approach involving endoscopic surveillance and prophylactic total gastrectomy.In this review, we discuss the range of predisposing germline HDGC variants and their effects, the mechanism of DGC initiation and growth, and current best practices for the diagnosis and management of this disease.Finally, we highlight emerging areas of research on the characterization, classification, and management of HDGC.","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41517846","pmcid":"PMC12802062","openalex_id":"https://openalex.org/W7117577882","authors":[],"funders":[{"funder_name":"New Zealand Health Research Council","grant_id":"22/301","title":null},{"funder_name":"No Stomach for Cancer","grant_id":"","title":null},{"funder_name":"Save Our Stomachs","grant_id":"","title":null},{"funder_name":"No Stomach for Cancer","grant_id":"","title":null},{"funder_name":"Save Our Stomachs","grant_id":"","title":null}],"total_grants":5,"fwci":0.407,"citation_percentile":0.66671414,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"http://jgc-online.org/Synapse/Data/PDFData/1100JGC/jgc-26-e5.pdf","host_type":"journal"},{"url":"http://jgc-online.org/Synapse/Data/PDFData/1100JGC/jgc-26-e5.pdf","host_type":"publisher"},{"url":"https://jgc-online.org/pdf/10.5230/jgc.2026.26.e5","host_type":"publisher"},{"url":"https://jgc-online.org/DOIx.php?id=10.5230/jgc.2026.26.e5","host_type":"publisher"},{"url":"https://doi.org/10.5230/jgc.2026.26.e5","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41517846","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12802062/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12802062","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12802062?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Wnt/β-catenin signaling in development and cancer","Cancer Cells and Metastasis","HER2/EGFR in Cancer Research","Humans","Stomach Neoplasms","Cadherins","Antigens, CD","alpha Catenin","Genetic Predisposition to Disease","Germ-Line Mutation","Neoplastic Syndromes, Hereditary","Gastrectomy"],"mesh_terms":["Gastrectomy","Humans","Neoplastic Syndromes, Hereditary","Stomach Neoplasms","Antigens, CD","Cadherins","Germ-Line Mutation","Carcinoma, Signet Ring Cell","Genetic Predisposition to Disease","alpha Catenin"],"keywords":["Cancer","Adherens junction","Germline","Germline mutation","Breast cancer","CDH1","Invasive lobular carcinoma","Cell","Cell of origin","Gastrectomy","Cadherins","Signet Ring Cell Carcinoma","Catenins","Neoplastic Syndromes"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T03:53:59.695527Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}