[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-330769-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-330769-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","targeted-and-shallow-whole-genome-sequencing-identifies-therapeutic-opportunities-in-p53abn-endometrial-cancers","Targeted and Shallow Whole-Genome Sequencing - Identifies Therapeutic Opportunities in p53abn Endometrial Cancers","","Shallow whole-genome sequencing combined with targeted profiling is used to uncover copy-number aberration patterns in p53abn endometrial cancers. The study identifies five distinct CN signatures in 187 cases, links signature 5 to BRCA1/2 copy-number loss and HGSOC-like HRD biology, and associates other signatures with high ploidy and amplification events. Clinical correlations include survival differences and HER2-linked poor outcomes, while frequent mutations include PPP2R1A and FBXW7.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/targeted-and-shallow-whole-genome-sequencing-identifies-therapeutic-opportunities-in-p53abn-endometrial-cancers/330769/",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/targeted-and-shallow-whole-genome-sequencing-identifies-therapeutic-opportunities-in-p53abn-endometrial-cancers/330769.png","ImageObject",300,407,{"name":42,"@type":43},"Hazel","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-05","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",5,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main goal of using shallow whole-genome sequencing in p53abn endometrial cancers?","Question",{"text":63,"@type":64},"To detect copy-number aberration patterns and apply them to improve prognostic stratification and reveal therapeutic opportunities beyond existing classification methods.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How many copy-number signatures were identified, and what was their clinical significance?",{"text":68,"@type":64},"Five distinct CN signatures were found. Signature 5 related to BRCA1/2 copy-number loss with HRD-like features, while signatures 1–3 showed differing associations with overall survival.",{"name":70,"@type":61,"acceptedAnswer":71},"Which molecular alterations were frequently observed and linked to outcomes?",{"text":72,"@type":64},"CCNE1 and ERBB2/HER2 amplifications were common, with ERBB2/HER2 associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the most frequent.","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},330769,1790193838,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,100,105,110,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"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":55,"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":111,"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,"preview_page_count":4},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","Targeted and Shallow Whole-Genome Sequencing  \nIdentifies Therapeutic Opportunities in p53abn  \nEndometrial Cancers  \nAmy Jamieson1, Juliana Sobral de Barros2, Dawn R. Cochrane2, J. Maxwell Douglas2, Sameer Shankar2, Branden J. Lynch2, Samuel Leung2, Spencer Martin3, Janine Senz2, Amy Lum2, Yvette Drew1,  \nC. Blake Gilks3, David G. Huntsman2,3, and Jessica N. McAlpine1  \nABSTRACT  \n◥  \nPurpose: Shallow whole-genome sequencing (sWGS) can detect copy-number (CN) aberrations. In high-grade serous ovarian cancer (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers to identify additional prognostic stratification and therapeutic opportunities.  \nExperimental Design: sWGS and targeted panel sequencing was performed on formalin-fixed, paraffin-embedded p53abn endometrial cancers. CN alterations, mutational data and CN signatures were derived, and associations to clinicopathologic and outcomes data were assessed.  \nResults: In 187 p53abn endometrial cancers, 5 distinct CN signatures were identified. Signature5was associated with BRCA1/2 CN loss with features similar to HGSOC HRD signature. Twentytwo percent of potential HRD cases were identified, 35 patients with  \nsignature 5, and 8 patients with BRCA1/2 somatic mutations. Signatures 3 and 4 were associated with a high ploidy state, and CCNE1, ERBB2, and MYC amplifications, with mutations in PIK3CA enriched in signature 3 . We observed improved overall survival (OS) for patients with signature 2 and worse OS for signatures 1 and 3 . Twenty-eight percent of patients had CCNE1 amplification and this subset was enriched with carcinosarcomahistotype. Thirty-four percent of patients, across all histotypes, had ERBB2 amplification and/or HER2 overexpression on IHC, which was associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the top 5 most common mutations.  \nConclusions: sWGS and targeted sequencing identified therapeutic opportunities in 75% of patients with p53abn endometrial cancer. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn endometrial cancers.  \nIntroduction  \nThe discovery of the four molecular subtypes of endometrial carcinoma by the Cancer Genome Atlas (TCGA) in 2013 has transformed care in this disease site, including a change from dependence on histomorphology to a system of molecular classification to provide reproducible categorization, stratify risk of recurrence, and direct adjuvant therapies. The copy-number high (CN-high) subtype identified by TCGA had poor outcomes (\u003C50% 5-year overall survival, OS) and was characterized by high somatic CN alterations (SCNA), low mutation rate, nearly ubiquitous TP53 mutations, and molecular similarities to high-grade serous ovarian cancer (HGSOC) and basal-like breast cancer ( 1) . Following the discovery by TCGA, two  \n1Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, Canada. 2Department of Molecular Oncology, University of British Columbia, Vancouver, Canada. 3Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.  \nA. Jamieson, D. R. Cochrane, and J. Sobral de Barros contributed equally to this article as co-first authors, while J. N. McAlpine and D. G. Huntsman contributed equally as senior authors.  \nCorresponding Author: Jessica N. McAlpine, University of British Columbia, 2775 Laurel Street, Vancouver, BC, Canada, V5Z1M9 . E-mail:  \njessica.mcalpine@vch.ca  \nClin Cancer Res 2024;30:2461–74  \ndoi: 10.1158/1078-0432 . CCR-23-3689  \nThis open access article is distributed under the Creative Commons AttributionNonCommercial-NoDerivatives 4 . 0 International (CC BY-NC-ND 4 . 0) license.  \n􀀂2024The Authors;Published by the American Association for Cancer Research  \nresearch groups independently worked to develop","cbCaih4FNPg5ykUT","https://ap.wps.com/l/cbCaih4FNPg5ykUT","pdf",10073110,14,"English","# Abstract\n## Purpose\n## Experimental Design\n## Results\n## Conclusions\n# Introduction\n## TCGA molecular subtypes and clinical implications\n## Need for further stratification and targeted options","[{\"question\":\"What is the main goal of using shallow whole-genome sequencing in p53abn endometrial cancers?\",\"answer\":\"To detect copy-number aberration patterns and apply them to improve prognostic stratification and reveal therapeutic opportunities beyond existing classification methods.\"},{\"question\":\"How many copy-number signatures were identified, and what was their clinical significance?\",\"answer\":\"Five distinct CN signatures were found. Signature 5 related to BRCA1/2 copy-number loss with HRD-like features, while signatures 1–3 showed differing associations with overall survival.\"},{\"question\":\"Which molecular alterations were frequently observed and linked to outcomes?\",\"answer\":\"CCNE1 and ERBB2/HER2 amplifications were common, with ERBB2/HER2 associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the most frequent.\"}]","Targeted and Shallow Whole-Genome Sequencing - Identifies Therapeutic Opportunities in p53abn Endometrial Cancers | PDF",1789989999,35]