[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-349175-105":59,"doc-detail-349175-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","integrated-germline-and-somatic-molecular-profiling-to-detect-cancer-predisposition-has-a-high-clinical-impact-in-poor-prognosis-pediatric-cancer","Integrated Germline and Somatic Molecular Profiling to Detect Cancer Predisposition Has a High Clinical Impact in Poor-Prognosis Pediatric Cancer","","Role of germline predisposition in pediatric cancer is increasingly recognized, yet the best approach to identifying cancer predisposing germline pathogenic variants (GPV) in children and their prevalence among pediatric cancer cases remains unclear. A national pediatric precision oncology program evaluated GPV prevalence and diagnostic yield across different testing strategies, using prospective rapid-turnaround whole-genome and transcriptome profiling in 496 children with poor-prognosis cancer.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/integrated-germline-and-somatic-molecular-profiling-to-detect-cancer-predisposition-has-a-high-clinical-impact-in-poor-prognosis-pediatric-cancer/349175/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/integrated-germline-and-somatic-molecular-profiling-to-detect-cancer-predisposition-has-a-high-clinical-impact-in-poor-prognosis-pediatric-cancer/349175.png","ImageObject",300,407,{"name":92,"@type":93},"Terk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What study question does the research address?","Question",{"text":112,"@type":113},"It examines how to identify cancer-predisposing germline pathogenic variants (GPV) in children and how often such GPVs occur among children with cancer, within a national pediatric precision oncology program.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What methodology was used to profile the patients?",{"text":117,"@type":113},"The study used prospective rapid-turnaround whole-genome and whole-transcriptome profiling in 496 consecutively recruited children with poor-prognosis cancer.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key results regarding GPV detection?",{"text":121,"@type":113},"Integrated tumor–germline molecular profiling identified GPVs in 15.5% of patients, with an incremental GPV yield of 7.9% over standard care, and cascade testing supported de novo origins in 21% of tested families.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},349175,1790146045,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099525198933,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Integrated Germline and Somatic Molecular Profiling to Detect Cancer Predisposition Has a High Clinical Impact in Poor-Prognosis Pediatric Cancer  \nNoemi A. Fuentes-Bolanos1,2,3, Eliza K. Courtney1,2,3, Chelsea Mayoh1,2, Meera Warby1,3,  \nLoretta M.S. Lau1,2,3, Marie Wong-Erasmus1,2, Dong-Anh Khuong-Quang4,5, Paulette Barahona1, Bhavna Padhye6,7, Naomi Warren1, Sam El-Kamand1,2, Sheena Nunag1, Pamela Ajuyah8, Alexandra Sherstyuk1, Ann-Kristin Altekoester1, Ashleigh Sullivan9, Nicola Poplawski10,11, Catherine Kiraly-Borri12, Sarah O’Sullivan12, Helen Mar Fan13, Rozanna Alli13, Lisette Curnow14, Kanika Bhatia4, Antoinette Anazodo1,2,3,15, Toby N. Trahair1,2,3, Marion K. Mateos1,2,3,  \nJordan R. Hansford16,17, Hetal Dholaria18,19,20, Sarah Josephi-Taylor21,22, Andrew S. Moore9,  \nWayne Nicholls9, Nicholas G. Gottardo18,19, Peter Downie23,24,26, Seong-Lin Khaw4,5, Heather Tapp16,17, Geoffrey McCowage6, Luciano Dalla-Pozza6, Frank Alvaro25, Paul J. Wood23,26, Vanessa Tyrrell1,2, Michelle Haber1,2, Mark J. Cowley1,2, Paul G. Ekert1,2,5,27, Glenn M. Marshall1,2,3, Judy Kirk28,29, Katherine Tucker2,3,15, Mark Pinese1,2, and David S. Ziegler1,2,3  \n|  |  | A |  | B | S |  | T | R |  | A |  | C | T |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |\n|  | Purpose: The role of germline predisposition in pediatric cancer is increasingly recognized. However, the optimal approach to identifying cancer predisposing germline pathogenic variants (GPV) in children, and even the prevalence of GPVs among children with cancer, remain unclear. We examined GPV prevalence and diagnostic yield of different test approaches within a national pediatric precision oncology program.\u003Cbr>Experimental Design: We performed prospective rapidturnaround whole-genome and -transcriptome profiling of 496 consecutively recruited children with poor-prognosis cancer to identify genetic variants linked to cancer risk.\u003Cbr>Results: Integration of tumor and germline molecular profiling identified GPVs in 15.5% of patients, an incremental GPV yield of 7.9% above that detected by standard care. Although the cancer\u003Cbr>􀀶 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | type was outside the recognized phenotypic spectrum for 43.7% of reported GPVs, 63.2% of these were clinically actionable. Integrated germline-tumor analysis increased the GPV detection rate by 8.5%, informed germline interpretation in 14.3% of patients with GPVs, and provided biological insight into tumor etiology, together highlighting the value of integrated analyses. Cascade testing in first-degree relatives confirmed that the GPV was de novo in 21% of tested families. Within inherited GPVs (73.9%), 47.8% had direct implications for risk management recommendations in the relevant parent.\u003Cbr>Conclusions: Our findings establish the clinical benefit and feasibility of integrated tumor–germline whole-genome screening to detect GPVs in children with poor-prognosis cancers and their first-degree relatives. |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | ","cbCaibjD49ftkRgh","https://ap.wps.com/l/cbCaibjD49ftkRgh","pdf",6022671,13,"English","# Purpose\n## Experimental Design\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What study question does the research address?\",\"answer\":\"It examines how to identify cancer-predisposing germline pathogenic variants (GPV) in children and how often such GPVs occur among children with cancer, within a national pediatric precision oncology program.\"},{\"question\":\"What methodology was used to profile the patients?\",\"answer\":\"The study used prospective rapid-turnaround whole-genome and whole-transcriptome profiling in 496 consecutively recruited children with poor-prognosis cancer.\"},{\"question\":\"What were the key results regarding GPV detection?\",\"answer\":\"Integrated tumor–germline molecular profiling identified GPVs in 15.5% of patients, with an incremental GPV yield of 7.9% over standard care, and cascade testing supported de novo origins in 21% of tested families.\"}]","Integrated Germline and Somatic Molecular Profiling to Detect Cancer Predisposition Has a High Clinical Impact in Poor-Prognosis Pediatric Cancer | PDF",1790082078,33]