{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:36:09Z","timestamp":1789788969417,"version":"4.0.1"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T00:00:00Z","timestamp":1683936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Gastric cancer (GC) has long been a \u2018Cinderella\u2019 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 carriers and 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.<\/jats:p>","DOI":"10.3390\/genes14051077","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T08:31:36Z","timestamp":1684139496000},"page":"1077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2113-8503","authenticated-orcid":false,"given":"Mariarosaria","family":"Calvello","sequence":"first","affiliation":[{"name":"Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Marabelli","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-4548","authenticated-orcid":false,"given":"Sara","family":"Gandini","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Marino","sequence":"additional","affiliation":[{"name":"Clinic Unit of Oncogenomics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loris","family":"Bernard","sequence":"additional","affiliation":[{"name":"Clinic Unit of Oncogenomics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Dal Molin","sequence":"additional","affiliation":[{"name":"Clinic Unit of Oncogenomics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Di Cola","sequence":"additional","affiliation":[{"name":"Clinic Unit of Oncogenomics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Zanzottera","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9269-0146","authenticated-orcid":false,"given":"Giovanni","family":"Corso","sequence":"additional","affiliation":[{"name":"Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"},{"name":"European Cancer Prevention Organization (ECP), 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-0704","authenticated-orcid":false,"given":"Nicola","family":"Fazio","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-8527","authenticated-orcid":false,"given":"Lorenzo","family":"Gervaso","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"},{"name":"Molecular Medicine Program, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Fumagalli Romario","sequence":"additional","affiliation":[{"name":"Digestive Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-4804","authenticated-orcid":false,"given":"Massimo","family":"Barberis","sequence":"additional","affiliation":[{"name":"Clinic Unit of Oncogenomics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-1688","authenticated-orcid":false,"given":"Aliana","family":"Guerrieri-Gonzaga","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Bertario","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-4108","authenticated-orcid":false,"given":"Davide","family":"Serrano","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-2128","authenticated-orcid":false,"given":"Bernardo","family":"Bonanni","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101404","DOI":"10.1016\/j.eclinm.2022.101404","article-title":"The current and future incidence and mortality of gastric cancer in 185 countries, 2020\u20132040: A population-based modelling study","volume":"47","author":"Morgan","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Morgado-Diaz, J.A. 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