[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-380996-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-380996-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","p53-protects-against-formation-of-extrahepatic-biliary-precancerous-lesions-in-the-context-of-oncogenic-kras","p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras","","KRAS and TP53 mutations are commonly found in extrahepatic biliary cancer, where they act as independent risk factors for poor prognosis. The precise contribution of p53 to extrahepatic biliary tumorigenesis has remained unclear. Using mice with simultaneous Kras activation and p53 inactivation, the study identifies biliary neoplasms resembling human biliary precancerous lesions. However, p53 loss alone does not drive these lesions into invasive cancer during the observation window, including with added Wnt pathway activation. Overall, p53 is shown to protect against formation of extrahepatic biliary precancerous lesions under oncogenic Kras.",{"@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/p53-protects-against-formation-of-extrahepatic-biliary-precancerous-lesions-in-the-context-of-oncogenic-kras/380996/",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/p53-protects-against-formation-of-extrahepatic-biliary-precancerous-lesions-in-the-context-of-oncogenic-kras/380996.png","ImageObject",300,407,{"name":42,"@type":43},"Olivia Brown","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What mutations are frequently associated with extrahepatic biliary cancer in this study?","Question",{"text":63,"@type":64},"KRAS and TP53 mutations are frequently observed in extrahepatic biliary cancer. The document notes that KRAS and TP53 mutations are independent risk factors for poor prognosis.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does simultaneous Kras activation and p53 inactivation affect biliary lesions in mice?",{"text":68,"@type":64},"Simultaneous activation of Kras and inactivation of p53 induces biliary neoplasms in mice that resemble human biliary intraepithelial neoplasia and intracholecystic papillarytubular neoplasm.",{"name":70,"@type":61,"acceptedAnswer":71},"Does p53 inactivation alone promote progression to invasive cancer in the oncogenic Kras context?",{"text":72,"@type":64},"No. The document states that p53 inactivation was not sufficient for precancerous lesions to progress into invasive cancer within the observation period, including when Wnt signaling was additionally activated.","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},380996,1790792567,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,109,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"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":55,"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":33,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":123},16904993612988,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","[www.oncotarget.com](www.oncotarget.com) Oncotarget, 2023, Vol. 14, pp: 276-279  \nEditorial  \np53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras  \nMunemasa Nagao, Kenta Mizukoshi, Shinnosuke Nakayama, Mio Namikawa, Yukiko Hiramatsu, Takahisa Maruno, Yuki Nakanishi, Tatsuaki Tsuruyama, Akihisa Fukuda and Hiroshi Seno  \nABSTRACT  \nKRAS and TP53 mutations are frequently observed in extrahepatic biliary cancer.  \nMutations of KRAS and TP53 are independent risk factors for poor prognosis in biliary cancer. However, the exact role of p53 in the development of extrahepatic biliary cancer remains elusive. In this study, we found that simultaneous activation of Kras and inactivation of p53 induces biliary neoplasms that resemble human biliary intraepithelial neoplasia in the extrahepatic bile duct and intracholecystic papillarytubular neoplasm in the gall bladder in mice. However, inactivation of p53 was not sufficient for the progression of biliary precancerous lesions into invasive cancer in the context of oncogenic Kras within the observation period. This was also the case in the context of additional activation of the Wnt signaling pathway. Thus, p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras.  \nBiliary tract cancer (BTC) includes cholangiocarcinoma (CCA) and gall bladder carcinoma (GBC) . According to the World Health Organization (WHO) databases, the global mortality for CCA increased worldwide [1] . The 5-year survival rate ofbiliary cancer remains only 5% to 15%[2, 3] . Recently, biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB) were defined as precursor lesions of invasive adenocarcinoma by the WHO classification [4–6] . BilIN is defined as a microscopically identifiable, pre-invasive neoplastic lesion of the biliary lining epithelia of the bile duct. IPNBis defined as a grossly visible, intraductal, preinvasive papillary or villous epithelial neoplasm covering fine fibrovascular stalks [7] . Papillary lesion like IPNBin the gall bladder (GB) is intracholecystic papillarytubular neoplasm (ICPN) [8] . However, the molecular mechanism of formation of these precursor lesions is not fully understood.  \nWhole-genome sequencing (WGS) studies have revealed high incidence of mutations in KRAS (17–18%) and TP53 (26–32%) in biliary cancer [9–11] . The incidence of KRAS mutation and TP53 mutation is 31.5% and 36.9%, respectively, in extrahepatic cholangiocarcinoma [12] . Mutations ofKRAS codon12 occurred in about 50% of early BilIN [13] . These findings suggest the possible roles of mutations in Krasand p53 in biliary tumorigenesis.  \nTo clarify the exact role of each molecule in which mutations are observed in biliary cancer, genetically engineered mouse model (GEM) is a powerful tool. Recently, we have shown that Hnf1bCreER mouse is one of the useful biliary-specific driver CreER mouse lines for gene manipulation in the extrahepatic biliary duct (EHBD) and GB, and that concurrent activation of the Kras and canonical Wnt pathways in the adult biliary epithelial cells induces BilIN and ICPN in the EHBD and GB, respectively [14] .  \nIt is well-known that p53 deficiency promotes the progression of precancerous lesions into invasive adenocarcinoma in the context of oncogenic Kras in the pancreas [15] . Therefore, we hypothesized that inactivation of p53 also promotes tumorigenesis in the extrahepatic biliary system. To determine whether mutation of KRAS or TP53 affects the progression of human cholangiocarcinoma, we first performed prognosis analyses of cholangiocarcinoma using the The Cancer Genome Atlas (TCGA) database. Overall survival was compared among the group with mutation of KRAS, group with mutation of TP53, and group without KRAS or TP53 mutation. Mutations of KRAS and TP53 were each negatively correlated with overall survival in human biliary cancer patients (Fi","cbCaitCh46pye56y","https://ap.wps.com/l/cbCaitCh46pye56y","pdf",1283393,"English","# Editorial\n## Abstract\n## Background and rationale\n## Whole-genome and human mutation findings\n## Mouse model approach (GEM)\n## Prognosis analysis using TCGA\n## Experimental design and figure description","[{\"question\":\"What mutations are frequently associated with extrahepatic biliary cancer in this study?\",\"answer\":\"KRAS and TP53 mutations are frequently observed in extrahepatic biliary cancer. The document notes that KRAS and TP53 mutations are independent risk factors for poor prognosis.\"},{\"question\":\"How does simultaneous Kras activation and p53 inactivation affect biliary lesions in mice?\",\"answer\":\"Simultaneous activation of Kras and inactivation of p53 induces biliary neoplasms in mice that resemble human biliary intraepithelial neoplasia and intracholecystic papillarytubular neoplasm.\"},{\"question\":\"Does p53 inactivation alone promote progression to invasive cancer in the oncogenic Kras context?\",\"answer\":\"No. The document states that p53 inactivation was not sufficient for precancerous lesions to progress into invasive cancer within the observation period, including when Wnt signaling was additionally activated.\"}]","p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras | PDF",1790243074]