{"id":52880,"date":"2024-01-30T15:27:31","date_gmt":"2024-01-30T07:27:31","guid":{"rendered":"https:\/\/csi.nus.edu.sg\/?p=52880"},"modified":"2024-01-30T17:12:49","modified_gmt":"2024-01-30T09:12:49","slug":"spatiotemporal-genomic-profiling-of-intestinal-metaplasia-reveals-clonal-dynamics-of-gastric-cancer-progression-cancer-cell-oct-2023","status":"publish","type":"post","link":"https:\/\/csi.nus.edu.sg\/spatiotemporal-genomic-profiling-of-intestinal-metaplasia-reveals-clonal-dynamics-of-gastric-cancer-progression-cancer-cell-oct-2023\/","title":{"rendered":"Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression (Cancer Cell, Oct 2023)"},"content":{"rendered":"<p><span class=\"authors-list-item \">Kie Kyon Huang<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Haoran Ma<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Roxanne Hui Heng Chong<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Tomoyuki Uchihara<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Benedict Shi Xiang Lian<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Feng Zhu<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Taotao Sheng<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>3<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Supriya Srivastava<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Su Ting Tay<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Raghav Sundar<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>4<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Angie Lay Keng Tan<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Xuewen Ong<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Minghui Lee<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Shamaine Wei Ting Ho<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>3<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Tom Lesluyes<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>5<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Hassan Ashktorab<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>6<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Duane Smoot<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>7<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Peter Van Loo<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>8<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Joy Shijia Chua<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>2<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Kalpana Ramnarayanan<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>1<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Louis Ho Shing Lau<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>9<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Takuji Gotoda<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>10<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Hyun Soo Kim<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>11<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Tiing Leong Ang<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>12<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Christopher Khor<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>13<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Jonathan Wei Jie Lee<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>14<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Stephen Kin Kwok Tsao<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>15<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Wei Lyn Yang<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>15<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Ming Teh<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>16<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Hyunsoo Chung<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>17<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Jimmy Bok Yan So<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>18<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Khay Guan Yeoh<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>19<\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \">Patrick Tan<sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span>20<\/sup><span class=\"semicolon\">;\u00a0<\/span><\/span><span class=\"authors-list-item \">Singapore Gastric Cancer Consortium<\/span><\/p>\n<h3 class=\"title\">Affiliations<\/h3>\n<ul class=\"item-list\">\n<li id=\"full-view-affiliation-1\" data-affiliation-id=\"full-view-affiliation-1\"><sup class=\"key\">1<\/sup>Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore.<\/li>\n<li id=\"full-view-affiliation-2\" data-affiliation-id=\"full-view-affiliation-2\"><sup class=\"key\">2<\/sup>Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.<\/li>\n<li id=\"full-view-affiliation-3\" data-affiliation-id=\"full-view-affiliation-3\"><sup class=\"key\">3<\/sup>Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.<\/li>\n<li id=\"full-view-affiliation-4\" data-affiliation-id=\"full-view-affiliation-4\"><sup class=\"key\">4<\/sup>Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Department of Haematology-Oncology, National University Health System, Singapore 119074, Singapore.<\/li>\n<li id=\"full-view-affiliation-5\" data-affiliation-id=\"full-view-affiliation-5\"><sup class=\"key\">5<\/sup>The Francis Crick Institute, London, UK.<\/li>\n<li id=\"full-view-affiliation-6\" data-affiliation-id=\"full-view-affiliation-6\"><sup class=\"key\">6<\/sup>Department of Medicine, Howard University, Washington, DC, USA.<\/li>\n<li id=\"full-view-affiliation-7\" data-affiliation-id=\"full-view-affiliation-7\"><sup class=\"key\">7<\/sup>Department of Internal Medicine, Meharry Medical College, Nashville, TN, USA.<\/li>\n<li id=\"full-view-affiliation-8\" data-affiliation-id=\"full-view-affiliation-8\"><sup class=\"key\">8<\/sup>The Francis Crick Institute, London, UK; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<\/li>\n<li id=\"full-view-affiliation-9\" data-affiliation-id=\"full-view-affiliation-9\"><sup class=\"key\">9<\/sup>Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.<\/li>\n<li id=\"full-view-affiliation-10\" data-affiliation-id=\"full-view-affiliation-10\"><sup class=\"key\">10<\/sup>Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.<\/li>\n<li id=\"full-view-affiliation-11\" data-affiliation-id=\"full-view-affiliation-11\"><sup class=\"key\">11<\/sup>Department of Internal Medicine, Yonsei University Wonju College of Medicine, Seoul, Korea.<\/li>\n<li id=\"full-view-affiliation-12\" data-affiliation-id=\"full-view-affiliation-12\"><sup class=\"key\">12<\/sup>Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore 529889, Singapore.<\/li>\n<li id=\"full-view-affiliation-13\" data-affiliation-id=\"full-view-affiliation-13\"><sup class=\"key\">13<\/sup>Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore 169854, Singapore.<\/li>\n<li id=\"full-view-affiliation-14\" data-affiliation-id=\"full-view-affiliation-14\"><sup class=\"key\">14<\/sup>Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; iHealthtech, National University of Singapore, Singapore, Singapore; SynCTI, National University of Singapore, Singapore 117599, Singapore; Department of Gastroenterology & Hepatology, National University Hospital, Singapore 119074, Singapore.<\/li>\n<li id=\"full-view-affiliation-15\" data-affiliation-id=\"full-view-affiliation-15\"><sup class=\"key\">15<\/sup>Department of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore 308433, Singapore.<\/li>\n<li id=\"full-view-affiliation-16\" data-affiliation-id=\"full-view-affiliation-16\"><sup class=\"key\">16<\/sup>Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.<\/li>\n<li id=\"full-view-affiliation-17\" data-affiliation-id=\"full-view-affiliation-17\"><sup class=\"key\">17<\/sup>Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Electronic address: h.chung@snu.ac.kr.<\/li>\n<li id=\"full-view-affiliation-18\" data-affiliation-id=\"full-view-affiliation-18\"><sup class=\"key\">18<\/sup>Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Division of Surgical Oncology, National University Cancer Institute of Singapore (NCIS), Singapore, Singapore. Electronic address: jimmyso@nus.edu.sg.<\/li>\n<li id=\"full-view-affiliation-19\" data-affiliation-id=\"full-view-affiliation-19\"><sup class=\"key\">19<\/sup>Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Department of Gastroenterology & Hepatology, National University Hospital, Singapore 119074, Singapore. Electronic address: mdcykg@nus.edu.sg.<\/li>\n<li id=\"full-view-affiliation-20\" data-affiliation-id=\"full-view-affiliation-20\"><sup class=\"key\">20<\/sup>Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore; Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore; Singhealth\/Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Singapore 168752, Singapore. Electronic address: gmstanp@duke-nus.edu.sg.<\/li>\n<\/ul>\n<h2 class=\"title\">Abstract<\/h2>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<p>Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral\/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to transform to GC. By highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression, our results raise opportunities for GC precision prevention and interception.<\/p>\n<p><span class=\"id-label\" style=\"font-size: 16px;\">PMID:\u00a0<\/span><strong class=\"current-id\" style=\"font-size: 16px;\" title=\"PubMed ID\">37890493\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 <\/strong><span class=\"id-label\" style=\"font-size: 16px;\">DOI: <\/span><a class=\"id-link\" style=\"font-size: 16px; background-color: #ffffff;\" href=\"https:\/\/doi.org\/10.1016\/j.ccell.2023.10.004\" target=\"_blank\" rel=\"noopener\" data-ga-category=\"full_text\" data-ga-action=\"DOI\">10.1016\/j.ccell.2023.10.004<\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Kie Kyon Huang\u00a01,\u00a0Haoran Ma\u00a01,\u00a0Roxanne Hui Heng Chong\u00a02,\u00a0Tomoyuki Uchihara\u00a01,\u00a0Benedict Shi Xiang Lian\u00a01,\u00a0Feng Zhu\u00a02,\u00a0Taotao Sheng\u00a03,\u00a0Supriya Srivastava\u00a02,\u00a0Su Ting Tay\u00a01,\u00a0Raghav Sundar\u00a04,\u00a0Angie Lay Keng Tan\u00a01,\u00a0Xuewen Ong\u00a01,\u00a0Minghui Lee\u00a01,\u00a0Shamaine Wei Ting Ho\u00a03,\u00a0Tom Lesluyes\u00a05,\u00a0Hassan Ashktorab\u00a06,\u00a0Duane Smoot\u00a07,\u00a0Peter Van Loo\u00a08,\u00a0Joy …<\/p>\n<p class=\"read-more\"> <a class=\"\" href=\"https:\/\/csi.nus.edu.sg\/spatiotemporal-genomic-profiling-of-intestinal-metaplasia-reveals-clonal-dynamics-of-gastric-cancer-progression-cancer-cell-oct-2023\/\"> <span class=\"screen-reader-text\">Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression (Cancer Cell, Oct 2023)<\/span> Read More »<\/a><\/p>\n","protected":false},"author":9,"featured_media":52881,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","footnotes":""},"categories":[56,16,23],"tags":[],"class_list":["post-52880","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-56","category-latest-happenings","category-research"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.6 - 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