[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-350513-105":59,"doc-detail-350513-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","developmental-timing-distinguishes-pediatric-and-adult-cancers-through-retention-and-rewiring-mechanisms","Developmental Timing Distinguishes Pediatric and Adult Cancers Through Retention and Rewiring Mechanisms","","Oncogenic mutations can produce different outcomes depending on the developmental stage of the tissue in which they arise. The work proposes a unifying model: early-life events promote retention and stabilization of transient embryo–fetal transcriptional and epigenetic programs, while later-life mutations more often drive rewiring through stepwise transcriptional and chromatin remodeling. This temporal dimension explains age-dependent differences in lineage trajectories, tumor behavior, mutational landscapes, and therapeutic response. Incorporating developmental timing may refine cancer modeling and prognostic risk stratification, revealing stage-specific vulnerabilities.",{"@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/developmental-timing-distinguishes-pediatric-and-adult-cancers-through-retention-and-rewiring-mechanisms/350513/",{"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/developmental-timing-distinguishes-pediatric-and-adult-cancers-through-retention-and-rewiring-mechanisms/350513.png","ImageObject",300,407,{"name":92,"@type":93},"Franzy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What core idea does the paper propose about oncogenic mutations?","Question",{"text":112,"@type":113},"Oncogenic mutations can have fundamentally different consequences depending on the developmental state of the tissue where they occur, linking developmental timing to oncogenic potency and downstream tumor biology.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do early-life and later-life mutations differ mechanistically?",{"text":117,"@type":113},"Early-life oncogenic events promote retention and stabilization of transient embryo–fetal transcriptional and epigenetic programs, whereas later-life mutations more often require rewiring and reactivation through stepwise transcriptional and chromatin remodeling.",{"name":119,"@type":110,"acceptedAnswer":120},"Why can childhood and adult cancers show distinct behaviors and therapeutic responses?",{"text":121,"@type":113},"The temporal dimension helps explain differences in lineage trajectories, mutational landscapes, and therapeutic response even when tumors are initiated by the same genetic lesion.","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},350513,1790198004,{"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":8,"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},2336478945519,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Perspective [https://doi.org/10.1038/s41467-026-75182-7](https://doi.org/10.1038/s41467-026-75182-7)  \nDevelopmental timing distinguishes pediatric and adult cancers through retention and rewiring mechanisms  \nReceived: 11 January 2026  \n\n| Accepted: 23 June 2026 |\n| --- |\n| |\n| Check for updates |\n\nShayan Saniei 1,2 & Elvin Wagenblast 3,4,5,6,7,8   \nOncogenic mutations can have fundamentally different consequences depending on the developmental state of the tissue in which they arise. We propose a unifying model in which early-life oncogenic events promote retention, stabilization of transient embryo-fetal transcriptional and epigenetic programs, whereas later-life mutations more often require rewiring, reactivating suppressed oncofetal states through stepwise transcriptional and chromatin remodeling. This temporal dimension helps explain why childhood and adult cancers can follow distinct lineage trajectories, behaviors, and therapeutic responses, even when initiated by the same genetic lesion. Incorporating developmental timing into cancer modeling and risk stratification may improve prognostic resolution and reveal stage-specific vulnerabilities.  \nPediatric and adult tumors are distinguished by well-established molecular differences, including a markedly lower mutational burden in childhood and young adult cancers. Pediatric tumors are enriched for copy number alterations and structural variants1 rather than the accumulation of large numbers of point mutations, and fewer than half of recurrent pediatric alterations are represented in pan-adult mutational landscapes2. The tissue origins and cancer types most frequently observed across age groups are also distinct3. Adult cancers predominantly arise from epithelial compartments in the gastrointestinal tract, lung, breast, and reproductive organs, whereas pediatric cancers are disproportionately composed of brain tumors4,5, hematological malignancies2, and embryonal/endocrine cancers6. Additionally, many pediatric solid tumors originate from mesodermal, ectodermal, and endodermal tissues that are still developing during embryonic life, transient structures that are no longer present in adulthood7. Together, these contrasts argue that oncogenic selection operates on different cellular substrates across the lifespan, with distinct sets of transforming events becoming advantageous in different tissues and developmental windows.  \nA defining yet often underappreciated feature of pediatric cancers is that many initiating lesions arise during the most developmentally dynamic stages of human life3. Mounting evidence supports a fetal8–13, and in some cases embryonic14,15, origin for multiple malignancies, including leukemias, blastomas, and Wilms tumor. During development, cellular identity, chromatin accessibility, transcriptional circuitry, and niche dependence are rapidly remodeled. As a result, the same genetic lesion can confer a radically different selective advantage depending on when during development it occurs, even within the same lineage. This principle extends beyond pediatric cancers, as tumors across all ages can arise from stem or progenitor compartments, but these populations themselves traverse discrete maturation states with different proliferative capacity, metabolic wiring, differentiation potential, and epigenetic competence16,17. Here, we propose that developmental timing is a core determinant of oncogenic potency and downstream tumor biology. We recently established this principle experimentally in pediatric leukemia, where the same oncogenic lesion conferred different oncogenic potential and therapy responses depending on the  \n1Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2Tri-Institutional Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY, USA. 3Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4Department of Pediatrics, Division of Pediatric ","cbCaiv0jdFWX5hJ8","https://ap.wps.com/l/cbCaiv0jdFWX5hJ8","pdf",1356900,13,"English","# Background\n## Developmental stage-dependent oncogenic consequences\n## Molecular distinctions between pediatric and adult tumors\n# Proposed model\n## Retention of embryo–fetal programs\n## Rewiring and reactivation of suppressed states\n# Implications\n## Explaining age-specific mutational landscapes and responses\n## Opportunities for modeling, risk stratification, and vulnerabilities","[{\"question\":\"What core idea does the paper propose about oncogenic mutations?\",\"answer\":\"Oncogenic mutations can have fundamentally different consequences depending on the developmental state of the tissue where they occur, linking developmental timing to oncogenic potency and downstream tumor biology.\"},{\"question\":\"How do early-life and later-life mutations differ mechanistically?\",\"answer\":\"Early-life oncogenic events promote retention and stabilization of transient embryo–fetal transcriptional and epigenetic programs, whereas later-life mutations more often require rewiring and reactivation through stepwise transcriptional and chromatin remodeling.\"},{\"question\":\"Why can childhood and adult cancers show distinct behaviors and therapeutic responses?\",\"answer\":\"The temporal dimension helps explain differences in lineage trajectories, mutational landscapes, and therapeutic response even when tumors are initiated by the same genetic lesion.\"}]","Developmental Timing Distinguishes Pediatric and Adult Cancers Through Retention and Rewiring Mechanisms | PDF",1790089379,33]