[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332523-105":59,"doc-detail-332523-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","germline-functional-variants-contribute-to-somatic-mutation-and-outcomes-in-neuroblastoma","Germline functional variants contribute to somatic mutation and outcomes in neuroblastoma","","Germline genetic context can shape cancer development and evolution, yet childhood cancers may involve different mechanisms than adult-onset disease. Whole-exome sequencing of 125 neuroblastoma patients shows a positive correlation between putatively functional germline variant burden and somatic mutational burden, with higher germline burden linked to worse outcomes. Replication in an independent neuroblastoma cohort confirms associations with overall survival. Borderline enrichment in cancer predisposition genes supports a prognostic role, and integrating germline variants with clinical risk improves survival prediction, contrasting adult-onset cancer findings.",{"@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/germline-functional-variants-contribute-to-somatic-mutation-and-outcomes-in-neuroblastoma/332523/",{"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/germline-functional-variants-contribute-to-somatic-mutation-and-outcomes-in-neuroblastoma/332523.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of the study on neuroblastoma?","Question",{"text":112,"@type":113},"The study evaluates how putatively functional germline variants influence somatic mutation burden and patient outcomes in neuroblastoma, even when they do not directly raise disease risk.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the findings tested across cohorts?",{"text":117,"@type":113},"The authors performed whole-exome sequencing in a Korean neuroblastoma cohort and then replicated the analyses in an independent neuroblastoma cohort using WES data.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the relationship between germline variant burden and patient outcomes?",{"text":121,"@type":113},"Higher germline variant burden correlates with higher somatic mutational burden and worse overall survival outcomes, and it has prognostic significance when combined with clinical risk factors.","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},332523,1790093825,{"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":34,"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":41},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Article [https://doi.org/10.1038/s41467-024-52128-5](https://doi.org/10.1038/s41467-024-52128-5)  \nGermline functional variants contribute to somatic mutation and outcomes in neuroblastoma  \nReceived: 19 June 2023  \n\n| Accepted: 27 August 2024 |\n| --- |\n| |\n| Check for updates |\n\nEun Seop Seo 1,2,3,6, Ji Won Lee 1,6, Jinyeong Lim 3, Sunghwan Shin 4, Hee Won Cho1, Hee Young Ju1, Keon Hee Yoo1, Ki Woong Sung1  & Woong-Yang Park 2,3,5   \nGermline genetic context may play a significant role in the development and evolution of cancer, particularly in childhood cancers such as neuroblastoma. This study investigates the role of putatively functional germline variants in neuroblastoma, even if they do not directly increase disease risk. Our wholeexome sequencing analysis of 125 patients with neuroblastoma reveals a positive correlation between germline variant burden and somatic mutations. Moreover, patients with higher germline variant burden exhibit worse outcomes. Similar findings are observed in the independent neuroblastoma cohort where a higher germline variant burden correlates with a higher somatic mutational burden and a worse overall survival outcome. However, contrasting results emerge in adult-onset cancer, emphasizing the importance of germline genetics in neuroblastoma. The enrichment of putatively functional germline variants in cancer predisposition genes is borderline significant when compared to healthy populations (P = 0.077; Odds Ratio, 1.45; 95% confidence intervals, 0.94−2.21) and significantly more pronounced against adult-onset cancers (P =0.016; Odds Ratio, 2.13; 95% confidence intervals, 1.10−3.91). Additionally, the presence of these variants proves to have prognostic significance in neuroblastoma (log-rank P \u003C0.001), and combining germline with clinical risk factors notably improves survival predictions.  \nAs individuals age, the risk of accumulating mutations in their DNA increases significantly1,2. This accumulation of mutations is the primary reason that the risk of developing cancer increases over time3,4. However, the causes of childhood cancers such as neuroblastoma (the most common extracranial solid cancer in childhood5)may differ from those of adult-onset cancers6. Instead, inherited germline genetic variants may play a greater role in the development and presentation  \nof tumors, as children have fewer opportunities to accumulate mutations.  \nConsiderable research into germline genetics in neuroblastomas has revealed fundamental insights into predisposing germline variations. Genome-wide association studies (GWAS) have identified dozens of single-nucleotide polymorphisms associated with neuroblastoma risk7–9, while next-generation sequencing studies have  \n1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 2Department of Digital Health, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, South Korea. 3Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea. 4Department of Laboratory Medicine, Inje University Ilsan Paik Hospital, Goyang, South Korea. 5Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea. 6These authors contributed equally: Eun Seop Seo, Ji Won Lee.  \ne-mail: [kwsped@skku.edu](kwsped@skku.edu); [woongyang.park@samsung.com](woongyang.park@samsung.com)  \nreported several rare germline pathogenic variants in cancer predisposition genes (CPGs)10–13. However, variants identified from GWAS typically have modest effects14, and only a small proportion of patients with neuroblastoma exhibit known pathogenic germline variants in CPGs8,11,15,16. This indicates that most neuroblastomas occurred in the absence of highly penetrant germline variants. Additionally, previous studies have only focused on the predisposition to neuroblastoma associated with germline variants, but have overlooked the possibility that germline variants that do not po","cbCaiesKW9iuWjdv","https://ap.wps.com/l/cbCaiesKW9iuWjdv","pdf",1847788,12,"English","# Article overview\n## Study rationale and hypotheses\n## Germline variant burden and somatic mutational burden\n## Prognostic implications and risk prediction","[{\"question\":\"What is the main focus of the study on neuroblastoma?\",\"answer\":\"The study evaluates how putatively functional germline variants influence somatic mutation burden and patient outcomes in neuroblastoma, even when they do not directly raise disease risk.\"},{\"question\":\"How were the findings tested across cohorts?\",\"answer\":\"The authors performed whole-exome sequencing in a Korean neuroblastoma cohort and then replicated the analyses in an independent neuroblastoma cohort using WES data.\"},{\"question\":\"What is the relationship between germline variant burden and patient outcomes?\",\"answer\":\"Higher germline variant burden correlates with higher somatic mutational burden and worse overall survival outcomes, and it has prognostic significance when combined with clinical risk factors.\"}]","Germline functional variants contribute to somatic mutation and outcomes in neuroblastoma | PDF",1789998595]