{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T23:45:46Z","timestamp":1761176746219,"version":"build-2065373602"},"reference-count":87,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54GM133807"],"award-info":[{"award-number":["U54GM133807"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastric cancer (GC) is the fourth leading cause of cancer\u2010related death globally. Tumor profiling has revealed actionable gene alterations that guide treatment strategies and enhance survival. Among Hispanics living in Puerto Rico (PRH), GC ranks among the top 10 causes of cancer\u2010related death. However, the genetic mutational landscape of GC tumors from PRH remains unexplored. This study aimed to identify the most prevalent genetic alterations in GC tumors among PRH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined tumor mutational profiles of GC from 106 PRH between 2015 and 2022 (provided by CARIS Life Sciences and the Precision Oncology Alliance). Next\u2010generation sequencing data were available for 85 cases, which were categorized as hypermutated (\u2265\u200910 mutations\/megabase) or non\u2010hypermutated (&lt;\u200910 mutations\/megabase).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the non\u2010hypermutated cases, the most frequently mutated genes were\n                      <jats:italic>TP53<\/jats:italic>\n                      (56.9%),\n                      <jats:italic>CDH1<\/jats:italic>\n                      (29.2%),\n                      <jats:italic>ARID1A<\/jats:italic>\n                      (27.4%), and\n                      <jats:italic>KMT2D<\/jats:italic>\n                      (25.7%). Compared to TCGA, a majority non\u2010Hispanic cohort, PRH had significantly higher mutational frequencies in driver genes in both intestinal type (\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>CBLB<\/jats:italic>\n                      , and\n                      <jats:italic>MYH11<\/jats:italic>\n                      ) and diffuse type (\n                      <jats:italic>CDH1<\/jats:italic>\n                      ,\n                      <jats:italic>ARID1A<\/jats:italic>\n                      , and\n                      <jats:italic>KMT2D<\/jats:italic>\n                      ) GC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Intestinal\u2010type GC in PR aligns with the chromosomal instability (CIN) molecular classification, showing a higher frequency of\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations than TCGA, potentially indicating more aggressive tumor biology and poorer prognosis. Diffuse\u2010type GC showed higher\n                      <jats:italic>CDH1<\/jats:italic>\n                      mutations, correlating with the genomically stable (GS) classification, characterized by fewer chromosomal changes but significant genetic alterations, including those in\n                      <jats:italic>ARID1A<\/jats:italic>\n                      and\n                      <jats:italic>KMT2D<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study shows that the unique genetic landscape of GC tumors in this group may lead to more aggressive cases and affect treatment responses, contributing to higher mortality rates. The higher mutation rates in biomarkers related to prognosis and therapy suggest that further research might uncover additional susceptibility variants. This underscores the importance of including Hispanics in genomic studies to better understand the genetic pathways associated with the risk and progression of GC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71216","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T04:25:34Z","timestamp":1757478334000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Actionable Genes and Carcinogenic Pathways for Gastric Cancer in Latinos"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3289-9597","authenticated-orcid":false,"given":"Ingrid M.","family":"Montes\u2010Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Division of Clinical &amp; Translational Cancer Research, Medical Sciences Campus University of Puerto Rico Comprehensive Cancer Center  San Juan Puerto 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Medicine, Medical Sciences Campus University of Puerto Rico School of Medicine  San Juan Puerto Rico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia","family":"Cruz\u2010Correa","sequence":"additional","affiliation":[{"name":"Division of Clinical &amp; Translational Cancer Research, Medical Sciences Campus University of Puerto Rico Comprehensive Cancer Center  San Juan Puerto Rico"},{"name":"Division of Gastroenterology, Department of Medicine University of Puerto Rico School of Medicine  San Juan Puerto 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