[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-353750-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-353750-en":131},{"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","stk11-mutations-and-deletions-define-a-distinct-subtype-of-cervical-adenocarcinoma","STK11 mutations and deletions define a distinct subtype of cervical adenocarcinoma","","Between 10 and 20% of cervical cancers are adenocarcinomas with poorer five-year survival and higher recurrence. To uncover somatic drivers, whole-exome sequencing was performed on 308 invasive-disease cases from Guatemala and Venezuela. STK11 tumor suppressor mutations and deletions occur at higher frequency in adenocarcinoma than SCC, including deletions undetected by exome alone. STK11 alterations predict earlier onset, worse overall survival, and reduced response to immune checkpoint inhibitors, with evidence of pathway interaction with YAP1 and mutual exclusivity with PIK3CA.",{"@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/stk11-mutations-and-deletions-define-a-distinct-subtype-of-cervical-adenocarcinoma/353750/",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/stk11-mutations-and-deletions-define-a-distinct-subtype-of-cervical-adenocarcinoma/353750.png","ImageObject",300,407,{"name":42,"@type":43},"Miles","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",16,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What proportion of cervical cancers are adenocarcinomas in this study’s background?","Question",{"text":63,"@type":64},"Adenocarcinomas account for 10–20% of cervical cancers, with poorer five-year survival and higher recurrence.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was the genomic landscape of invasive cervical cancer assessed?",{"text":68,"@type":64},"Whole-exome sequencing was conducted on 308 subjects with invasive disease, followed by confirmation in external cohorts and additional whole-genome/SNP-array analyses.",{"name":70,"@type":61,"acceptedAnswer":71},"What clinical associations are linked to STK11 mutations and deletions?",{"text":72,"@type":64},"STK11 alterations are associated with younger age of onset, poorer overall survival, and poorer response to immune checkpoint inhibitors.","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},353750,1790231740,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":113,"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},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","medRxiv preprint doi: [https://doi.org/10.64898/2026.01.01.25343162](https://doi.org/10.64898/2026.01.01.25343162); this version posted January 4, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nThis article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available  \nfor use under a CC0 license.  \nSTK11 mutations and deletions define a distinct subtype of cervical adenocarcinoma  \nEmma Robinson 1,2, Elisabeth Murphy3, Anaseidy Albanez4, Sonam Tulsyan 1, Hong Lou2, Yi Xie 1, Weiyin Zhou2, Qian Yang 1, Tawnjerae Joe 1, Tongwu Zhang 1, Jia Liu2, Wen Luo2, Dongling Wu2, Herbert Higson2, Mathias Viard5, Mary Carrington5,6, Matt Oberley3, Douglas R. Stewart 1, Hesler Morales4,7, Lisa Mirabello 1, Enrique Alvirez8, Roberto Orozco7, Eduardo Gharzouzi9, Michael Dean 1*  \n1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA;  \n2 Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA,  \n3 Caris Life Sciences, Irving, TX, USA  \n4 Instituto de Cancerología (INCAN), Guatemala City, Guatemala  \n5 Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA, and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA  \n6 Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA  \n7 Hospital General San Juan de Dios, Guatemala City, Guatemala  \n8 Hospital Central Universitario \"Dr. Antonio M Pineda,\" Barquisimeto, Lara State, Venezuela, and Universidad Andino de Cusco, Cusco, Perú .  \n9 Integra Cancer Center, Guatemala City, Guatemala  \n*-correspondence to Dr. Michael Dean, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA; tel 301-219-4076, email  \n[deanm@mail.nih.gov](deanm@mail.nih.gov)  \nKey words: Cervical cancer, human papilloma virus, STK11 oncogene, adenocarcinoma, whole exome sequencing  \nRunning Title: A cervical adenocarcinoma subtype defined by STK11 mutation  \n1  \nNOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.  \nmedRxiv preprint doi: [https://doi.org/10.64898/2026.01.01.25343162](https://doi.org/10.64898/2026.01.01.25343162); this version posted January 4, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nThis article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available  \nfor use under a CC0 license.  \nAbstract  \nBetween 10 and 20% of cervical cancers are adenocarcinomas with poorer five-year survival and higher recurrence. To identify somatic alterations driving cervical cancer, we performed wholeexome sequencing of 308 subjects with invasive disease from Guatemala and Venezuela.  \nConsistent with other studies, there is a higher rate of TP53 mutations in adenocarcinomas versus squamous cell carcinomas (SCC), especially in HPV-negative tumors. We identified a higher rate of mutations and deletions (23%) in the STK11 tumor suppressor gene in adenocarcinomas versus SCC. This result was confirmed in the AACR Project Genie and Caris cohorts. Wholegenome sequencing and SNP-array data identified significant numbers of focal deletions on chr19p that disrupt STK11, undetected by exome sequencing. In one tumor, HPV integration disrupts STK11 . Chr19p is commonly deleted in cervical cancer, and we document a high rate of independent inversions, chromosomal translocations, and breakage-fusion-bridge events that provide the second hit to STK11 . Significantly, STK","cbCaiqv7oVXRmXt7","https://ap.wps.com/l/cbCaiqv7oVXRmXt7","pdf",612598,"English","# Abstract\n# Significance\n# Introduction","[{\"question\":\"What proportion of cervical cancers are adenocarcinomas in this study’s background?\",\"answer\":\"Adenocarcinomas account for 10–20% of cervical cancers, with poorer five-year survival and higher recurrence.\"},{\"question\":\"How was the genomic landscape of invasive cervical cancer assessed?\",\"answer\":\"Whole-exome sequencing was conducted on 308 subjects with invasive disease, followed by confirmation in external cohorts and additional whole-genome/SNP-array analyses.\"},{\"question\":\"What clinical associations are linked to STK11 mutations and deletions?\",\"answer\":\"STK11 alterations are associated with younger age of onset, poorer overall survival, and poorer response to immune checkpoint inhibitors.\"}]","STK11 mutations and deletions define a distinct subtype of cervical adenocarcinoma | PDF",1790107052,76]