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A Mono-Institutional Experience","","Gastric cancer remains a major global health burden, with risk shaped by known exposures and inherited predisposition syndromes. While single-gene testing historically focused on high-risk identification, multigene panel testing prompted debate about additional genes, particularly homologous recombination (HR) repair genes. This mono-institutional experience evaluated genetic counseling and testing in 54 patients, and extended multigene panel testing to 37, comparing variant yields across clinical features and family history.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/hereditary-gastric-cancer-single-gene-or-multigene-panel-testing-a-mono-institutional-experience/384745/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/hereditary-gastric-cancer-single-gene-or-multigene-panel-testing-a-mono-institutional-experience/384745.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why has multigene panel testing changed the approach to hereditary gastric cancer?","Question",{"text":112,"@type":113},"It expanded beyond single-gene testing to investigate whether additional genes contribute to risk, with special attention to homologous recombination (HR) repair genes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What was the testing experience reported for single-gene testing in the study?",{"text":117,"@type":113},"Among 54 gastric cancer patients, nine pathogenic variants were detected, and seven patients tested for unknown mutations carried a pathogenic variant in specific genes including CDH1 and MSH2.",{"name":119,"@type":110,"acceptedAnswer":120},"How did family history and Lynch-related tumors relate to the detection of pathogenic variants?",{"text":121,"@type":113},"The study found statistically significant differences in pathogenic variant detection between patients with and without family history of gastric cancer (p=0.045) and between those with and without Lynch-related tumors (p=0.036).","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},384745,1790669684,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Article  \nHereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience  \nMariarosaria Calvello 1, Monica Marabelli 1,*, Sara Gandini 2, Elena Marino 3, Loris Bernard 3, Matteo Dal Molin 3, Giulia Di Cola 3, Cristina Zanzottera 1, Giovanni Corso 4,5,6, Nicola Fazio 7, Lorenzo Gervaso 7,8, Uberto Fumagalli Romario 9, Massimo Barberis 3, Aliana Guerrieri-Gonzaga 1, Lucio Bertario 1, Davide Serrano 1 and Bernardo Bonanni 1  \nCitation: Calvello, M.; Marabelli, M.; Gandini, S.; Marino, E.; Bernard, L.; Dal Molin, M.; Di Cola, G.;  \nZanzottera, C.; Corso, G.; Fazio, N.; et al. Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience. Genes 2023, 14, 1077 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)genes14051077  \nAcademic Editor: Christos K. Kontos  \nReceived: 14 April 2023  \nRevised: 5 May 2023  \nAccepted: 11 May 2023  \nPublished: 13 May 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy  \n2 Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy  \n3 Clinic Unit of Oncogenomics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy  \n4 Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy  \n5 Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy  \n6 European Cancer Prevention Organization (ECP), 20122 Milan, Italy  \n7 Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy  \n8 Molecular Medicine Program, University of Pavia, 27100 Pavia, Italy  \n9 Digestive Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy  \n* [Correspondence: monica.marabelli@ieo.it](Correspondence: monica.marabelli@ieo.it)  \nAbstract: Gastric cancer (GC) has long been a `Cinderella' among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those pertaining to homologous recombination (HR) repair. We report our mono-institutional experience in genetic counseling and SGT for 54 GC patients, with the detection of nine pathogenic variants (PVs) (9/54:16.7%) . Seven out of ﬁfty (14%) patients who underwent SGT for unknown mutations were carriers of a PV in CDH1 (n = 3), BRCA2 (n = 2), BRCA1 (n = 1), and MSH2 (n = 1), while one patient (2%) carried two variants of unknown signiﬁcance (VUSs) . CDH1 and MSH2 emerged as genes involved in early-onset diffuse and later-onset intestinal GCs, respectively. We additionally conducted MGPT on 37 patients, identifying ﬁve PVs (13.5%), including three (3/5:60%) in an HR gene (BRCA2, ATM, RAD51D) and at least one VUS in 13 patients (35.1%) . Comparing PV carriersand non-carriers, we observed a statistically signiﬁcant difference in PVs between patients with and without family history of GC (p-value: 0.045) or Lynch-related tumors (p-value: 0.036) . Genetic counseling remains central to GC risk assessment. MGPT appeared advantageous in patients with unspeciﬁc phenotypes, although it led to challenging results.  \nKeywords: gastric cancer; multigene panel testing; BRCA1; BRCA2; CDH1; MSH2; hereditary diffuse gastric cancer syndrome; homologous recombination DNA repair genes  \n1. Introduction  \nGastric cancer (GC) still represents a signiﬁcant health problem worldwide. Despite a decrease in incidence and mortality","cbCaibzYAw6k4tYw","https://ap.wps.com/l/cbCaibzYAw6k4tYw","pdf",657447,13,"English","# Abstract\n# Introduction","[{\"question\":\"Why has multigene panel testing changed the approach to hereditary gastric cancer?\",\"answer\":\"It expanded beyond single-gene testing to investigate whether additional genes contribute to risk, with special attention to homologous recombination (HR) repair genes.\"},{\"question\":\"What was the testing experience reported for single-gene testing in the study?\",\"answer\":\"Among 54 gastric cancer patients, nine pathogenic variants were detected, and seven patients tested for unknown mutations carried a pathogenic variant in specific genes including CDH1 and MSH2.\"},{\"question\":\"How did family history and Lynch-related tumors relate to the detection of pathogenic variants?\",\"answer\":\"The study found statistically significant differences in pathogenic variant detection between patients with and without family history of gastric cancer (p=0.045) and between those with and without Lynch-related tumors (p=0.036).\"}]","Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience | PDF",1790264816,33]