[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-381423-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-381423-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","the-epigenetic-modifier-lysine-methyltransferase-2c-is-frequently-mutated-in-gastric-remnant-carcinoma","The epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma","","Gastric remnant carcinoma (GRC), arising in the stomach after partial gastrectomy, is a rare and aggressive gastric adenocarcinoma subtype. Whole-exome sequencing of 36 matched tumor–normal samples identified recurrent mutations in epigenetic modifiers, especially KMT2C, ARID1A, NSD1, and KMT2D, occurring in 61.11% of cases. Mutation signature analyses showed low microsatellite instability (MSI) frequency, confirmed by MSIsensor, MSI–PCR, and immunohistochemistry. Comparative profiling revealed a distinct mutation spectrum versus gastric adenocarcinoma (TCGA), with a higher KMT2C mutation rate.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/the-epigenetic-modifier-lysine-methyltransferase-2c-is-frequently-mutated-in-gastric-remnant-carcinoma/381423/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/the-epigenetic-modifier-lysine-methyltransferase-2c-is-frequently-mutated-in-gastric-remnant-carcinoma/381423.png","ImageObject",300,407,{"name":42,"@type":43},"Jordan Avery","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main focus of the study on gastric remnant carcinoma (GRC)?","Question",{"text":63,"@type":64},"The study investigates the genomic landscape of GRC and identifies recurrent mutations, with particular emphasis on the epigenetic modifier KMT2C.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were the genomic findings validated beyond the initial whole-exome sequencing cohort?",{"text":68,"@type":64},"Targeted deep sequencing (Target-seq) was performed on an additional 25 paired tumor–normal samples to verify the high KMT2C mutation frequency.",{"name":70,"@type":61,"acceptedAnswer":71},"What relationship did KMT2C mutations show with clinical and immune parameters?",{"text":72,"@type":64},"KMT2C mutations were associated with poor overall survival in both cohorts, and they correlated with immune-related favorable features, including higher CD3+ and CD8+ tumor-infiltrating lymphocytes and PD–L1 expression in GRC samples.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},381423,1790723035,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},1099523882367,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","The Journal of Pathology: Clinical Research  \nJ Pathol Clin Res September 2023; 9: 409–422 Published online 3 July 2023 in Wiley Online Library (wi[leyonlinelibrary.com](leyonlinelibrary.com). DOI: 10.1002/cjp2.335)[).](leyonlinelibrary.com). DOI: 10.1002/cjp2.335)[ DOI: 10.1002/cjp2.335](leyonlinelibrary.com). DOI: 10.1002/cjp2.335)  \nORIGINAL ARTICLE  \nThe epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma  \nBo Sun 1,2† , Haojie Chen3†, Jiawen Lao4†, Cong Tan5, Yue Zhang5, Zhen Shao3* and Dazhi Xu 1,2*  \n1 Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, PR China 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China  \n3CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China  \n4Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China 5Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, PR China  \n*Correspondence to: Zhen Shao, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China. E-mail: [shaozhen@picb.ac.cn](shaozhen@picb.ac.cn); Dazhi Xu, Department of Gastric  \nSurgery, Fudan University Shanghai Cancer Center, Shanghai 200030, [PR China. E-mail:](PR China. E-mail: xudzh@shca.org.cn)[ xudzh@shca.org.cn](PR China. E-mail: xudzh@shca.org.cn)  \n†These authors contributed equally to this work.  \nAbstract  \nGastric remnant carcinoma (GRC), which occurs in the stomach after partial gastrectomy, is a rare and aggressive form of gastric adenocarcinoma (GAC). Comprehensive profiling of genomic mutations in GRC could provide the basis for elucidating the origin and characteristics of this cancer. Herein, whole-exome sequencing (WES) was performed on 36 matched tumor–normal samples from patients with GRC and identified recurrent mutations in epigenetic modifiers, notably KMT2C, ARID1A, NSD1, and KMT2D, in 61.11% of cases. Mutational signature analysis revealed a low frequency of microsatellite instability (MSI) in GRC, which was further identified by MSIsensor, MSI-polymerase chain reaction, and immunohistochemistry analysis. Comparative analysis demonstrated that GRC had a distinct mutation spectrum compared to that of GAC in The Cancer Genome Atlas samples, with a significantly higher mutation rate of KMT2C. Targeted deep sequencing (Target-seq) of an additional 25 paired tumor–normal samples verified the high mutation frequency (48%) of KMT2C in GRC.  \nKMT2C mutations correlated with poor overall survival in both WES and Target-seq cohorts and were independent prognosticators in GRC. In addition, KMT2C mutations were positively correlated with favorable outcomes in immune checkpoint inhibitor-treated pan-cancer patients and associated with higher intratumoral CD3+, CD8+ tumor-infiltrating lymphocyte counts, and PD–L1 expression in GRC samples (p = 0.018, 0.092, 0.047, 0.010, and 0.034, respectively). Our dataset provides a platform for information and knowledge mining of the genomic characteristics of GRC and helps to frame new therapeutic approaches for this disease.  \nKeywords: gastric carcinoma; whole-exome sequencing; microsatellite instability; tumor microenvironment  \nReceived 27 July 2022; Revised 20 May 2023; Accepted 25 May 2023 No conflicts of interest were declared.  \nIntroduction  \nGastric remnant carcinoma (GRC) is a relatively rare malignancy that develops in the remnant stomach after partial gastrectomy, regardless of the initial pathology or reconstruction technique [1] . GRC has an incidence of 1–5% after gastrectomy. Due to adjacent organ invasion and extensive lymph node metastasis, GRChas an unfavorable prognosis [2], and improving its clinical outcome remains a challenge.  \nRecently, omics analy","cbCaimRQlOCmvokX","https://ap.wps.com/l/cbCaimRQlOCmvokX","pdf",5280767,14,"English","# Abstract\n# Introduction\n# Materials and methods","[{\"question\":\"What is the main focus of the study on gastric remnant carcinoma (GRC)?\",\"answer\":\"The study investigates the genomic landscape of GRC and identifies recurrent mutations, with particular emphasis on the epigenetic modifier KMT2C.\"},{\"question\":\"How were the genomic findings validated beyond the initial whole-exome sequencing cohort?\",\"answer\":\"Targeted deep sequencing (Target-seq) was performed on an additional 25 paired tumor–normal samples to verify the high KMT2C mutation frequency.\"},{\"question\":\"What relationship did KMT2C mutations show with clinical and immune parameters?\",\"answer\":\"KMT2C mutations were associated with poor overall survival in both cohorts, and they correlated with immune-related favorable features, including higher CD3+ and CD8+ tumor-infiltrating lymphocytes and PD–L1 expression in GRC samples.\"}]","The epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma | PDF",1790245229,35]