{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:12:59Z","timestamp":1784740379933,"version":"3.55.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":281,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Autonomous University of Mexico (UNAM) PAPIIT","award":["225224"],"award-info":[{"award-number":["225224"]}]},{"name":"National Autonomous University of Mexico(UNAM) PAPIIT","award":["IN219217"],"award-info":[{"award-number":["IN219217"]}]},{"name":"National Council for Science and Technology (CONACyT) Fondo Sectorial","award":["272573"],"award-info":[{"award-number":["272573"]}]},{"name":"National Council for Science and Technology (CONACyT) Fondo SEP","award":["285879"],"award-info":[{"award-number":["285879"]}]},{"name":"National Council for Science and Technology (CONACyT) National Laboratories","award":["315817"],"award-info":[{"award-number":["315817"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Gastric cancer (GC) is the fifth-leading cause of cancer-related mortality, with a 5-year survival rate less than 20%. It develops from preneoplastic lesions to adenocarcinoma, but these early genetic alterations remain poorly understood. Therefore, we aimed to identify early genetic drivers underlying the development of preneoplastic lesions and the initiation of gastric carcinogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We characterized preneoplastic and early gastric adenocarcinoma using 48 samples from 16 Guatemalan patients, a country with a high incidence of GC. We sequenced a panel of 127 genes to identify early genetic drivers and possible actionable targets.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified extensive genetic heterogeneity, including single nucleotide and copy number variations. After comparing our data with other studies, we identified TP53 and APC as the most mutated genes in preneoplastic lesions and early GC. Our mean tumor mutational burden was higher in diffuse (0.017 mutations\/Mb) and intestinal adenocarcinomas (0.015) than in chronic gastritis (0.005), and analysis of the mutational signatures revealed several processes acting at different stages of the disease. Signatures S15 (DNA mismatch repair deficiency) and S03 (homologous recombination deficiency) were more frequent in early adenocarcinoma than in chronic gastritis, intestinal metaplasia, necrosis, tubular adenoma, and atrophy. Notably, 10 of 16 patients (62.5%) had at least one actionable mutation in their preneoplastic lesions or gastric adenocarcinomas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We show that at the preneoplastic and earliest stages, GC is genetically heterogeneous and presents key cancer-driving mutations that may participate in neoplastic transformation and progression, with 62.5% of lesions having the potential for treatment. This study expands the limited research on early GC and highlights key opportunities for precision medicine in populations with high GC incidence.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/gastro\/goaf089","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T15:02:28Z","timestamp":1760022148000},"source":"Crossref","is-referenced-by-count":3,"title":["Genetic heterogeneity and key driver mutations in the preneoplastic and earliest stages of gastric cancer"],"prefix":"10.1093","volume":"13","author":[{"given":"Eduardo Alfonso","family":"Marroqu\u00edn-Estrada","sequence":"first","affiliation":[{"name":"School of Postgraduate Studies, Faculty of Medical Sciences, University of San Carlos of Guatemala , Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Mart\u00ednez-Gregorio","sequence":"additional","affiliation":[{"name":"National Laboratory of Health, Molecular Diagnosis and Environmental Effects on Chronic-Degenerative Diseases, Faculty of Higher Studies Iztacala , Tlalnepantla, State of Mexico,","place":["Mexico"]},{"name":"Biomedical Research Unit, Faculty of Higher Studies Iztacala, UNAM , Tlalnepantla, State of Mexico,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara Estela","family":"D\u00edaz-Vel\u00e1squez","sequence":"additional","affiliation":[{"name":"National Laboratory of Health, Molecular Diagnosis and Environmental Effects on Chronic-Degenerative Diseases, Faculty of Higher Studies Iztacala , Tlalnepantla, State of Mexico,","place":["Mexico"]},{"name":"Biomedical Research Unit, Faculty of Higher Studies Iztacala, UNAM , Tlalnepantla, State of Mexico,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Ambriz-Barrera","sequence":"additional","affiliation":[{"name":"National Laboratory of Health, Molecular Diagnosis and Environmental Effects on Chronic-Degenerative Diseases, Faculty of Higher Studies Iztacala , Tlalnepantla, State of Mexico,","place":["Mexico"]},{"name":"Biomedical Research Unit, Faculty of Higher Studies Iztacala, UNAM , Tlalnepantla, State of Mexico,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Emilio","family":"C\u00f3rdoba-Garc\u00eda","sequence":"additional","affiliation":[{"name":"National Laboratory of Health, Molecular Diagnosis and Environmental Effects on Chronic-Degenerative Diseases, Faculty of Higher Studies Iztacala , Tlalnepantla, State of Mexico,","place":["Mexico"]},{"name":"Biomedical Research Unit, Faculty of Higher Studies Iztacala, UNAM , Tlalnepantla, State of Mexico,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Itzel","family":"Hern\u00e1ndez-Romero","sequence":"additional","affiliation":[{"name":"National Laboratory of Health, Molecular Diagnosis and Environmental Effects on Chronic-Degenerative Diseases, Faculty of Higher Studies Iztacala , Tlalnepantla, State of Mexico,","place":["Mexico"]},{"name":"Biomedical Research Unit, Faculty of Higher Studies Iztacala, UNAM , Tlalnepantla, State of Mexico,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Ruiz De-La-Cruz","sequence":"additional","affiliation":[{"name":"National Laboratory of Health, Molecular Diagnosis and Environmental Effects on Chronic-Degenerative Diseases, Faculty of Higher Studies Iztacala , Tlalnepantla, State of Mexico,","place":["Mexico"]},{"name":"Biomedical Research Unit, Faculty of Higher Studies Iztacala, UNAM , Tlalnepantla, State of Mexico,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"C\u00e1ceres","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"School of Postgraduate Studies, Faculty of Medical Sciences, University of San Carlos of Guatemala , Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Rodolfo","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratories and Pathology, Roosevelt Hospital , Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Orellana","sequence":"additional","affiliation":[{"name":"Department of Pathology, Francisco Marroquin Medical School , Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Penados","sequence":"additional","affiliation":[{"name":"BIOLAB Laboratory , Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Richter","sequence":"additional","affiliation":[{"name":"BIOLAB Laboratory , Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelino","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Roosevelt Hospital , Guatemala City, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Vaca-Paniagua","sequence":"additional","affiliation":[{"name":"National Laboratory of Health, Molecular Diagnosis and Environmental Effects on Chronic-Degenerative Diseases, Faculty of Higher Studies Iztacala , Tlalnepantla, State of Mexico,","place":["Mexico"]},{"name":"Biomedical Research Unit, Faculty of Higher Studies Iztacala, UNAM , Tlalnepantla, State of 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