{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T22:29:08Z","timestamp":1786400948150,"version":"build-2736575974"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"33","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Histone-lysine N-methyltransferase 2 (KMT2) family proteins methylate lysine 4 on the histone H3 tail at important regulatory regions in the genome and thereby impart crucial functions through modulating chromatin structures and DNA accessibility. We aimed to identify the molecular profile of KMT2-MT oesophageal cancer (EC) and associations with patient outcomes. In our study,\n                    <jats:italic>KMT2<\/jats:italic>\n                    mutations were significantly associated with longer immunotherapy-related overall survival (OS) in the esophageal adenocarcinoma (EA) (21.42 vs 13.42 months, HR\u2009=\u20090.66, 95% CI: 0.50\u20130.88,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.004), but not in the esophageal squamous cell carcinoma (ESCC).\n                    <jats:italic>KMT2<\/jats:italic>\n                    mutations were significantly associated with microsatellite instability-high and higher tumor mutation burden in both EA and ESCC.\n                    <jats:italic>KMT2<\/jats:italic>\n                    -MT EA showed significantly higher mutation rates in\n                    <jats:italic>CIC<\/jats:italic>\n                    (13% vs 1.1%),\n                    <jats:italic>NF1<\/jats:italic>\n                    (12.5% vs 2.2%),\n                    <jats:italic>FBXW7<\/jats:italic>\n                    (12% vs 3.4%),\n                    <jats:italic>ATM<\/jats:italic>\n                    (11.5% vs 2.6%) and\n                    <jats:italic>BRCA1<\/jats:italic>\n                    (11.5% vs 1%, all q\u2009&lt;\u20090.05), compared to\n                    <jats:italic>KMT2<\/jats:italic>\n                    -wildtype (WT) tumors. Meanwhile, no significant mutational differences were observed between\n                    <jats:italic>KMT2<\/jats:italic>\n                    -MT and WT ESCC. Fat digestion and absorption, cholesterol metabolism and the infiltration of activated B cells were significantly enriched in\n                    <jats:italic>KMT2<\/jats:italic>\n                    -MT EA compared to\n                    <jats:italic>KMT2<\/jats:italic>\n                    -WT EA, but these results were not observed in the ESCC. This is the largest study to investigate the distinct molecular landscapes in KMT2-MT EC, characterized by higher tumor mutational burden, an increased frequency of microsatellite instability-high, and gene mutations involved in DNA damage repair and epigenetic regulation.\n                  <\/jats:p>","DOI":"10.1038\/s41388-026-03897-4","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T08:32:55Z","timestamp":1783758775000},"page":"3472-3478","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic analysis of oesophageal carcinoma (EC) identifies recurrent mutations in histone methyltransferases as a distinctive subset"],"prefix":"10.1038","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6931-0359","authenticated-orcid":false,"given":"Jingyuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Xiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Battaglin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1886-7070","authenticated-orcid":false,"given":"Hiroyuki","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Soni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0308-8223","authenticated-orcid":false,"given":"Richard M.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony F.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Grothey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy J.","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8613-1890","authenticated-orcid":false,"given":"Igor","family":"Astaturov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Weinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1607-1386","authenticated-orcid":false,"given":"Emil","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0066-2672","authenticated-orcid":false,"given":"Rachna T.","family":"Shroff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moh\u2019d","family":"Khushman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed E.","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davendra P. 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JX and MO are employees of Caris Life Sciences. AFS reports funding for research, travel, and the speakers bureau from Caris Life Sciences. BAW reports receiving honoraria from Bayer, Sirtex, Lilly, Taiho, and HalioDx. RMG reports receiving consulting fees from AbbVie, AdaptImmune, AstraZeneca, Bayer, Compass Therapeutics, Eisai, Focal Medical, GeneCentric, Genentech, G1Therapeutics, GSK, Haystack Oncology (Quest), Inspirion, IQVIA, Merck, Sorrento Therapeutics, Taiho, Takeda, and Valar Labs. All remaining authors have declared no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This study was conducted in accordance with the guidelines of the Declaration of Helsinki, Belmont Report, and U.S. Common Rule. In keeping with 45 CFR 46.101(b) (4), this study was performed utilizing retrospective, deidentified clinical data. Therefore, this study is considered IRB exempt, and no patient consent was necessary from the subjects (Sponsor Protocol No.: CCC-001-0320).","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}}]}}