{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:24:22Z","timestamp":1793874262128,"version":"4.6.1"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Histone methylation can affect chromosome structure and binding to other proteins, depending on the type of amino acid being modified and the number of methyl groups added, this modification may promote transcription of genes (H3K4me2, H3K4me3, and H3K79me3) or reduce transcription of genes (H3K9me2, H3K9me3, H3K27me2, H3K27me3, and H4K20me3). In addition, advances in tumor immunotherapy have shown that histone methylation as a type of protein post-translational modification is also involved in the proliferation, activation and metabolic reprogramming of immune cells in the tumor microenvironment. These post-translational modifications of proteins play a crucial role in regulating immune escape from tumors and immunotherapy. Lysine methyltransferases are important components of the post-translational histone methylation modification pathway. Lysine methyltransferase 2C (KMT2C), also known as MLL3, is a member of the lysine methyltransferase family, which mediates the methylation modification of histone 3 lysine 4 (H3K4), participates in the methylation of many histone proteins, and regulates a number of signaling pathways such as EMT, p53, Myc, DNA damage repair and other pathways. Studies of KMT2C have found that it is aberrantly expressed in many diseases, mainly tumors and hematological disorders. It can also inhibit the onset and progression of these diseases. Therefore, KMT2C may serve as a promising target for tumor immunotherapy for certain diseases. Here, we provide an overview of the structure of KMT2C, disease mechanisms, and diseases associated with KMT2C, and discuss related challenges.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1444923","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:30:25Z","timestamp":1722904225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["The modification role and tumor association with a methyltransferase: KMT2C"],"prefix":"10.3389","volume":"15","author":[{"given":"Yunjuan","family":"Jiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhao","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwen","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiateng","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.pharmthera.2018.06.013","article-title":"Post-translational modifications of transporters","volume":"192","author":"Czuba","year":"2018","journal-title":"Pharmacol Ther"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-0602-4_12","article-title":"Protein modification and autophagy activation","volume":"1206","author":"Wang","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.stem.2020.12.009","article-title":"Histone crotonylation promotes mesoendodermal commitment of human embryonic stem cells","volume":"28","author":"Fang","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1122","article-title":"BAF155 methylation drives metastasis by hijacking super-enhancers and subverting anti-tumor immunity","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4402","DOI":"10.3390\/cancers13174402","article-title":"Therapeutic potential of targeting the SUMO pathway in cancer","volume":"13","author":"Kukkula","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.04.002","article-title":"Post-translational regulations of PD-L1 and PD-1: Mechanisms and opportunities for combined immunotherapy","volume":"85","author":"Dai","year":"2022","journal-title":"Semin Cancer Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41571-022-00601-9","article-title":"Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics","volume":"19","author":"Yamaguchi","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"a019505","DOI":"10.1101\/cshperspect.a019505","article-title":"Epigenetic determinants of cancer","volume":"8","author":"Baylin","year":"2016","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41392-020-00252-1","article-title":"The role of histone methylation in the development of digestive cancers: a potential direction for cancer management","volume":"5","author":"Chen","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2506","article-title":"Molecular pathways: metabolic control of histone methylation and gene expression in cancer","volume":"23","author":"Tran","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1101\/gad.255182.114","article-title":"Chromatin signatures of cancer","volume":"29","author":"Morgan","year":"2015","journal-title":"Genes Dev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9780","article-title":"Epigenetic balance of gene expression by Polycomb and COMPASS families","volume":"352","author":"Piunti","year":"2016","journal-title":"Science"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3554","article-title":"Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer","volume":"14","author":"Plass","year":"2013","journal-title":"Nat Rev Genet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1101\/gad.1499407","article-title":"pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene","volume":"21","author":"Kotake","year":"2007","journal-title":"Genes Dev"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1151","article-title":"SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells","volume":"6","author":"Hamamoto","year":"2004","journal-title":"Nat Cell Biol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature13320","article-title":"SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer","volume":"510","author":"Mazur","year":"2014","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.214577","article-title":"DOT1L inhibitor EPZ-5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLL-rearranged leukemia cells","volume":"350","author":"Klaus","year":"2014","journal-title":"J Pharmacol Exp Ther"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255104","article-title":"Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling","volume":"345","author":"Herz","year":"2014","journal-title":"Science"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.01.017","article-title":"Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase","volume":"25","author":"Kubicek","year":"2007","journal-title":"Mol Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2011.06.011","article-title":"Structural basis of substrate methylation and inhibition of SMYD2","volume":"19","author":"Ferguson","year":"2011","journal-title":"Structure"},{"key":"B22","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.cell.2012.03.025","article-title":"SnapShot: Histone lysine methylase complexes","volume":"149","author":"Mohan","year":"2012","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1146\/annurev-biochem-051710-134100","article-title":"The COMPASS family of histone H3K4 methylases: mechanisms of regulation in development and disease pathogenesis","volume":"81","author":"Shilatifard","year":"2012","journal-title":"Annu Rev Biochem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231473398","article-title":"COMPASS: a complex of proteins associated with a trithorax-related SET domain protein","volume":"98","author":"Miller","year":"2001","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3929","article-title":"Hijacked in cancer: the KMT2 (MLL) family of methyltransferases","volume":"15","author":"Rao","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1101\/gad.201327.112","article-title":"Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3\/Mll4","volume":"26","author":"Herz","year":"2012","journal-title":"Genes Dev"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01181-13","article-title":"The MLL3\/MLL4 branches of the COMPASS family function as major histone H3K4 monomethylases at enhancers","volume":"33","author":"Hu","year":"2013","journal-title":"Mol Cell Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nature12634","article-title":"Mutational landscape and significance across 12 major cancer types","volume":"502","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2291","article-title":"Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators","volume":"44","author":"Fujimoto","year":"2012","journal-title":"Nat Genet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nature11143","article-title":"Whole-genome analysis informs breast cancer response to aromatase inhibition","volume":"486","author":"Ellis","year":"2012","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-470559","article-title":"Exome sequencing identifies an MLL3 gene germ line mutation in a pedigree of colorectal cancer and acute myeloid leukemia","volume":"121","author":"Li","year":"2013","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/ng.907","article-title":"Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder","volume":"43","author":"Gui","year":"2011","journal-title":"Nat Genet"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.03.016","article-title":"MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia","volume":"25","author":"Chen","year":"2014","journal-title":"Cancer Cell"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.11.028","article-title":"FOXA1 Directs H3K4 Monomethylation at Enhancers via Recruitment of the Methyltransferase MLL3","volume":"17","author":"Jozwik","year":"2016","journal-title":"Cell Rep"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.048","article-title":"Mammary-stem-cell-based somatic mouse models reveal breast cancer drivers causing cell fate dysregulation","volume":"16","author":"Zhang","year":"2016","journal-title":"Cell Rep"},{"key":"B37","doi-asserted-by":"publisher","first-page":"R103","DOI":"10.1186\/gb-2011-12-10-r103","article-title":"Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer","volume":"12","author":"Kloosterman","year":"2011","journal-title":"Genome Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nature16952","article-title":"Structural basis for activity regulation of MLL family methyltransferases","volume":"530","author":"Li","year":"2016","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1528-1","article-title":"Structural basis of nucleosome recognition and modification by MLL methyltransferases","volume":"573","author":"Xue","year":"2019","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.molcel.2017.04.018","article-title":"Mll3 and mll4 facilitate enhancer RNA synthesis and transcription from promoters independently of H3K4 monomethylation","volume":"66","author":"Dorighi","year":"2017","journal-title":"Mol Cell"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.21.9737","article-title":"The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins","volume":"92","author":"Saha","year":"1995","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0034-6","article-title":"Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy","volume":"24","author":"Wang","year":"2018","journal-title":"Nat Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.molcel.2006.12.014","article-title":"Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark","volume":"25","author":"Ruthenburg","year":"2007","journal-title":"Mol Cell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nature18325","article-title":"Replication fork stability confers chemoresistance in BRCA-deficient cells","volume":"535","author":"Ray Chaudhuri","year":"2016","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902873106","article-title":"A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4","volume":"106","author":"Lee","year":"2009","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01503","article-title":"H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation","volume":"2","author":"Lee","year":"2013","journal-title":"Elife"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2013.12.005","article-title":"Replicative DNA polymerase mutations in cancer","volume":"24","author":"Heitzer","year":"2014","journal-title":"Curr Opin Genet Dev"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgr285","article-title":"Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort","volume":"33","author":"Duell","year":"2012","journal-title":"Carcinogenesis"},{"key":"B49","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12935-018-0523-1","article-title":"MLL2\/KMT2D and MLL3\/KMT2C expression correlates with disease progression and response to imatinib mesylate in chronic myeloid leukemia","volume":"18","author":"Rabello D do","year":"2018","journal-title":"Cancer Cell Int"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.clbc.2016.11.005","article-title":"Expression levels of KMT2C and SLC20A1 identified by information-theoretical analysis are powerful prognostic biomarkers in estrogen receptor-positive breast cancer","volume":"17","author":"Sato","year":"2017","journal-title":"Clin Breast Cancer"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/cancers4030904","article-title":"Molecular and epigenetic mechanisms of MLL in human leukemogenesis","volume":"4","author":"Ballabio","year":"2012","journal-title":"Cancers (Basel)"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162515","article-title":"Loss of mll3 catalytic function promotes aberrant myelopoiesis","volume":"11","author":"Arcipowski","year":"2016","journal-title":"PloS One"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5130-y","article-title":"Aberrant DNA methylation of acute myeloid leukemia and colorectal cancer in a Chinese pedigree with a MLL3 germline mutation","volume":"37","author":"Yang","year":"2016","journal-title":"Tumour Biol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12943-016-0500-z","article-title":"Mutation of epigenetic regulators TET2 and MLL3 in patients with HTLV-I-induced acute adult T-cell leukemia","volume":"15","author":"Yeh","year":"2016","journal-title":"Mol Cancer"},{"key":"B55","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13072-019-0283-8","article-title":"Aberrant methylation-mediated downregulation of lncRNA SSTR5-AS1 promotes progression and metastasis of laryngeal squamous cell carcinoma","volume":"12","author":"Wang","year":"2019","journal-title":"Epigenet Chromatin"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2013.01.022","article-title":"Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol","volume":"425","author":"Bhan","year":"2013","journal-title":"J Mol Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv214","article-title":"(GAS5)\/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL\/COMPASS-like complexes","volume":"43","author":"He","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S187540","article-title":"MLL3 promotes the senescence of esophageal squamous cell carcinoma","volume":"12","author":"Xia","year":"2019","journal-title":"Onco Targets Ther"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108997","article-title":"Association between histone lysine methyltransferase KMT2C mutation and clinicopathological factors in breast cancer","volume":"116","author":"Chen","year":"2019","journal-title":"BioMed Pharmacother"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0481","article-title":"Reduced expression of histone methyltransferases KMT2C and KMT2D correlates with improved outcome in pancreatic ductal adenocarcinoma","volume":"76","author":"Dawkins","year":"2016","journal-title":"Cancer Res"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846821","article-title":"The lysine-specific methyltransferase KMT2C\/MLL3 regulates DNA repair components in cancer","volume":"20","author":"Rampias","year":"2019","journal-title":"EMBO Rep"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1101\/gad.303768.117","article-title":"Histone H3K4 methylation-dependent and -independent functions of Set1A\/COMPASS in embryonic stem cell self-renewal and differentiation","volume":"31","author":"Sze","year":"2017","journal-title":"Genes Dev"},{"key":"B63","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.devcel.2019.04.033","article-title":"Stem cell proliferation is kept in check by the chromatin regulators kismet\/CHD7\/CHD8 and trr\/MLL3\/4","volume":"49","author":"Gervais","year":"2019","journal-title":"Dev Cell"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1679","article-title":"KMT2C mutations in diffuse-type gastric adenocarcinoma promote epithelial-to-mesenchymal transition","volume":"24","author":"Cho","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1177\/11769351231161480","article-title":"A computational approach to predict the role of genetic alterations in methyltransferase histones genes with implications in liver cancer","volume":"22","author":"Aravena","year":"2023","journal-title":"Cancer Inform"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001155","article-title":"Recurrent mutations in APC and CTNNB1 and activated wnt\/\u03b2-catenin signaling in intraductal papillary neoplasms of the bile duct: A whole exome sequencing study","volume":"42","author":"Fujikura","year":"2018","journal-title":"Am J Surg Pathol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01439","article-title":"Genomic features and clinical characteristics of adolescents and young adults with cholangiocarcinoma","volume":"9","author":"Feng","year":"2019","journal-title":"Front Oncol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.322","article-title":"A system for detecting high impact-low frequency mutations in primary tumors and metastases","volume":"37","author":"Anjanappa","year":"2018","journal-title":"Oncogene"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80854","article-title":"MLL3 regulates the CDKN2A tumor suppressor locus in liver cancer","volume":"12","author":"Zhu","year":"2023","journal-title":"Elife"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1210\/me.2011-1198","article-title":"Requirement for MLL3 in p53 regulation of hepatic expression of small heterodimer partner and bile acid homeostasis","volume":"25","author":"Kim","year":"2011","journal-title":"Mol Endocrinol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.4238\/2014.September.12.18","article-title":"Association of MLL3 expression with prognosis in gastric cancer","volume":"13","author":"Li","year":"2014","journal-title":"Genet Mol Res"},{"key":"B72","article-title":"A missense mutation (S3660L) in MLL3 gene influences risk of gastric cancer","volume":"19","author":"Li","year":"2014","journal-title":"J BUON"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.7.4239","article-title":"Mll3 genetic variants affect risk of gastric cancer in the chinese han population","volume":"14","author":"Li","year":"2013","journal-title":"Asian Pac J Cancer Prev"},{"key":"B74","doi-asserted-by":"publisher","first-page":"4586","DOI":"10.3390\/cancers13184586","article-title":"Mutations in epigenetic regulation genes in gastric cancer","volume":"13","author":"Nemtsova","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.18632\/aging.v15i3","article-title":"Comparison of the mutation patterns between tumor tissue and cell-free DNA in stage IV gastric cancer","volume":"15","author":"Kung","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S172710","article-title":"Difference of molecular alterations in HER2-positive and HER2-negative gastric cancers by whole-genome sequencing analysis","volume":"10","author":"Zhou","year":"2018","journal-title":"Cancer Manag Res"},{"key":"B77","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1136\/gutjnl-2018-318070","article-title":"Multiplex profiling of peritoneal metastases from gastric adenocarcinoma identified novel targets and molecular subtypes that predict treatment response","volume":"69","author":"Wang","year":"2020","journal-title":"Gut"},{"key":"B78","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s40364-020-00241-0","article-title":"KMT2A\/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors","volume":"8","author":"Zhang","year":"2020","journal-title":"biomark Res"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.335","article-title":"The epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma","volume":"9","author":"Sun","year":"2023","journal-title":"J Pathol Clin Res"},{"key":"B80","doi-asserted-by":"publisher","first-page":"3934","DOI":"10.3390\/ijms20163934","article-title":"The immune landscape of thyroid cancer in the context of immune checkpoint inhibition","volume":"20","author":"Varricchi","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1177\/20552076221133699","article-title":"Mutations in lysine methyltransferase 2C and PEG3 are associated with tumor mutation burden, prognosis, and antitumor immunity in pancreatic adenocarcinoma patients","volume":"8","author":"Huang","year":"2022","journal-title":"Digit Health"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/nature25459","article-title":"Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes","volume":"554","author":"Mueller","year":"2018","journal-title":"Nature"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903387","article-title":"Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer","volume":"381","author":"Golan","year":"2019","journal-title":"N Engl J Med"},{"key":"B84","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.tibs.2013.12.004","article-title":"KRAS: feeding pancreatic cancer proliferation","volume":"39","author":"Bryant","year":"2014","journal-title":"Trends Biochem Sci"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.02.059","article-title":"Carcinogenesis of pancreatic ductal adenocarcinoma","volume":"158","author":"Storz","year":"2020","journal-title":"Gastroenterology"},{"key":"B86","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nature16965","article-title":"Genomic analyses identify molecular subtypes of pancreatic cancer","volume":"531","author":"Bailey","year":"2016","journal-title":"Nature"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0245-4","article-title":"Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer","volume":"17","author":"Buscail","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3581","article-title":"Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma","volume":"28","author":"Philip","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.5009\/gnl18355","article-title":"Comprehensive cancer panel sequencing defines genetic diversity and changes in the mutational characteristics of pancreatic cancer patients receiving neoadjuvant treatment","volume":"13","author":"Yoon","year":"2019","journal-title":"Gut Liver"},{"key":"B90","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1158\/2159-8290.CD-ND2021-0107","article-title":"Researchers strive to refine TMB","volume":"11","year":"2021","journal-title":"Cancer Discovery"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2023.102051","article-title":"Sequencing paired tumor DNA and white blood cells improves circulating tumor DNA tracking and detects pathogenic germline variants in localized colon cancer","volume":"8","author":"Gimeno-Valiente","year":"2023","journal-title":"ESMO Open"},{"key":"B92","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1007\/s13258-023-01408-3","article-title":"Comparison of genetic variation between primary colorectal cancer and metastatic peritoneal cancer","volume":"45","author":"Shin","year":"2023","journal-title":"Genes Genomics"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1285508","article-title":"Comprehensive genomic profiling reveals prognostic signatures and insights into the molecular landscape of colorectal cancer","volume":"13","author":"Yang","year":"2023","journal-title":"Front Oncol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"79","DOI":"10.21037\/jgo-21-28","article-title":"Prognosis model of colorectal cancer patients based on NOTCH3, KMT2C, and CREBBP mutations","volume":"12","author":"Liu","year":"2021","journal-title":"J Gastrointest Oncol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2023.07.008","article-title":"Deciphering brain metastasis stem cell properties from colorectal cancer highlights specific stemness signature and shared molecular features","volume":"16","author":"Desette","year":"2023","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.148","article-title":"Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia","volume":"117","author":"Chakrabarty","year":"2017","journal-title":"Br J Cancer"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023320","article-title":"Frequent alteration of MLL3 frameshift mutations in microsatellite deficient colorectal cancer","volume":"6","author":"Watanabe","year":"2011","journal-title":"PloS One"},{"key":"B98","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s13148-020-00863-z","article-title":"Restoration of KMT2C\/MLL3 in human colorectal cancer cells reinforces genome-wide H3K4me1 profiles and influences cell growth and gene expression","volume":"12","author":"Larsson","year":"2020","journal-title":"Clin Epigenet"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15716","article-title":"Association of KMT2C\/D loss-of-function variants with response to immune checkpoint blockades in colorectal cancer","volume":"114","author":"Liu","year":"2023","journal-title":"Cancer Sci"},{"key":"B100","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.canlet.2019.05.024","article-title":"COMPASS Ascending: Emerging clues regarding the roles of MLL3\/KMT2C and MLL2\/KMT2D proteins in cancer","volume":"458","author":"Fagan","year":"2019","journal-title":"Cancer Lett"},{"key":"B101","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1164\/rccm.201902-0294OC","article-title":"Genomic underpinnings of tumor behavior in in situ and early lung adenocarcinoma","volume":"201","author":"Qian","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"B102","doi-asserted-by":"publisher","first-page":"20243","DOI":"10.1038\/s41598-020-76791-y","article-title":"Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib\/gefitinib","volume":"10","author":"Shang","year":"2020","journal-title":"Sci Rep"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1839","article-title":"Comprehensive analysis of age-related somatic mutation profiles in Chinese young lung adenocarcinoma patients","volume":"8","author":"Yang","year":"2019","journal-title":"Cancer Med"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.04.012","article-title":"Metastasis organotropism: redefining the congenial soil","volume":"49","author":"Gao","year":"2019","journal-title":"Dev Cell"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.908759","article-title":"Genomic features of organ-specific metastases in lung adenocarcinoma","volume":"12","author":"Feng","year":"2022","journal-title":"Front Oncol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21778","article-title":"Metastatic patterns in adenocarcinoma","volume":"106","author":"Hess","year":"2006","journal-title":"Cancer"},{"key":"B107","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.lungcan.2014.07.020","article-title":"Metastatic sites and survival in lung cancer","volume":"86","author":"Riihim\u00e4ki","year":"2014","journal-title":"Lung Cancer"},{"key":"B108","doi-asserted-by":"publisher","first-page":"694","DOI":"10.21037\/atm-21-1555","article-title":"Whole-exome sequencing identifies somatic mutations associated with lung cancer metastasis to the brain","volume":"9","author":"Liu","year":"2021","journal-title":"Ann Transl Med"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01497","article-title":"First-line immunotherapy for non-small-cell lung cancer","volume":"40","author":"Reck","year":"2022","journal-title":"J Clin Oncol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.3390\/cancers14112816","article-title":"Mutations in KMT2C, BCOR and KDM5C predict response to immune checkpoint blockade therapy in non-small cell lung cancer","volume":"14","author":"Liu","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S381825","article-title":"Molecular characteristics and the effect of KRAS mutation on the prognosis of immunotherapy in non-small cell lung cancer in Xinjiang, China","volume":"15","author":"Gu","year":"2022","journal-title":"Onco Targets Ther"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000381","article-title":"Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study","volume":"8","author":"Bai","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-017-0099-6","article-title":"A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer","volume":"37","author":"Fantini","year":"2018","journal-title":"Oncogene"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0078-z","article-title":"The long tail of oncogenic drivers in prostate cancer","volume":"50","author":"Armenia","year":"2018","journal-title":"Nat Genet"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2024.01.015","article-title":"Germline variants in early and late-onset Brazilian prostate cancer patients","author":"Coelho","year":"2024","journal-title":"Urol Oncol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-020-00302-3","article-title":"TP53 alterations of hormone-na\u00efve prostate cancer in the Chinese population","volume":"24","author":"Liu","year":"2021","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.32604\/or.2023.028321","article-title":"Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients","volume":"31","author":"Zhu","year":"2023","journal-title":"Oncol Res"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1111\/ajco.13124","article-title":"Association between human papillomavirus infection and prostate cancer: A global systematic review and meta-analysis","volume":"15","author":"Moghoofei","year":"2019","journal-title":"Asia Pac J Clin Oncol"},{"key":"B119","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1186\/s40001-023-01207-2","article-title":"Genomic alterations related to HPV infection status in a cohort of Chinese prostate cancer patients","volume":"28","author":"Lang","year":"2023","journal-title":"Eur J Med Res"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24554","article-title":"Genetic mutations in smoking-associated prostate cancer","volume":"83","author":"Elshafei","year":"2023","journal-title":"Prostate"},{"key":"B121","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s12943-022-01542-8","article-title":"KMT2C methyltransferase domain regulated INK4A expression suppresses prostate cancer metastasis","volume":"21","author":"Limberger","year":"2022","journal-title":"Mol Cancer"},{"key":"B122","doi-asserted-by":"publisher","first-page":"19304","DOI":"10.1038\/s41598-020-74580-1","article-title":"Targeted sequencing reveals the somatic mutation landscape in a Swedish breast cancer cohort","volume":"10","author":"Mathioudaki","year":"2020","journal-title":"Sci Rep"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.4048\/jbc.2020.23.e41","article-title":"Analysis of circulating tumor DNA to predict neoadjuvant therapy effectiveness and breast cancer recurrence","volume":"23","author":"Hao","year":"2020","journal-title":"J Breast Cancer"},{"key":"B124","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13058-020-01328-0","article-title":"Clinical implications of prospective genomic profiling of metastatic breast cancer patients","volume":"22","author":"van Geelen","year":"2020","journal-title":"Breast Cancer Res"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0273-5","article-title":"KMT2C mediates the estrogen dependence of breast cancer through regulation of ER\u03b1 enhancer function","volume":"37","author":"Gala","year":"2018","journal-title":"Oncogene"},{"key":"B126","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1530\/JME-11-0078","article-title":"HOXC10 is overexpressed in breast cancer and transcriptionally regulated by estrogen via involvement of histone methylases MLL3 and MLL4","volume":"48","author":"Ansari","year":"2012","journal-title":"J Mol Endocrinol"},{"key":"B127","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1186\/s12935-020-01500-8","article-title":"XIST lost induces ovarian cancer stem cells to acquire taxol resistance via a KMT2C-dependent way","volume":"20","author":"Huang","year":"2020","journal-title":"Cancer Cell Int"},{"key":"B128","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0378-1119(02)00392-X","article-title":"MLL3, a new human member of the TRX\/MLL gene family, maps to 7q36, a chromosome region frequently deleted in myeloid leukaemia","volume":"284","author":"Ruault","year":"2002","journal-title":"Gene"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198056","article-title":"The genetic landscape of the childhood cancer medulloblastoma","volume":"331","author":"Parsons","year":"2011","journal-title":"Science"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12019","article-title":"The role of chromatin remodeling in medulloblastoma","volume":"23","author":"Jones","year":"2013","journal-title":"Brain Pathol"},{"key":"B131","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s40478-020-01066-6","article-title":"Clinical and mutational profiles of adult medulloblastoma groups","volume":"8","author":"Wong","year":"2020","journal-title":"Acta Neuropathol Commun"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjx056","article-title":"EZH2-, CHD4-, and IDH-linked epigenetic perturbation and its association with survival in glioma patients","volume":"9","author":"Zhang","year":"2017","journal-title":"J Mol Cell Biol"},{"key":"B133","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ajhg.2012.05.003","article-title":"Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability","volume":"91","author":"Kleefstra","year":"2012","journal-title":"Am J Hum Genet"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.2217\/epi.15.1","article-title":"Disrupted intricacy of histone H3K4 methylation in neurodevelopmental disorders","volume":"7","author":"Vallianatos","year":"2015","journal-title":"Epigenomics"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1444923\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:30:29Z","timestamp":1722904229000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1444923\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":134,"alternative-id":["10.3389\/fimmu.2024.1444923"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1444923","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]},"article-number":"1444923"}}