[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-331296-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-331296-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","genomic-patterns-of-somatic-mutations-provide-new-prognostic-therapeutic-and-biological-insights-in-cancer","Genomic patterns of somatic mutations provide new prognostic, therapeutic, and biological insights in cancer","","Genomic patterns of somatic mutations in individual cancers can reveal molecular state and enable prognostic and therapeutic marker discovery. The summarized work by Barbour and colleagues analyzes bladder cancer to connect ERCC2 mutation status with distinct mutational signatures, biological pathways, and predictive tools. The study focuses on APOBEC-associated SBS2 and SBS13 patterns, showing how ERCC2 mutations shift APOBEC mutation proportions and genomic distribution. Results support ERCC2 as an independent predictor of prognosis and link signature analysis with clinical actionable decisions.",{"@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/genomic-patterns-of-somatic-mutations-provide-new-prognostic-therapeutic-and-biological-insights-in-cancer/331296/",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/genomic-patterns-of-somatic-mutations-provide-new-prognostic-therapeutic-and-biological-insights-in-cancer/331296.png","ImageObject",300,407,{"name":42,"@type":43},"Levi","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-07","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How do mutational landscapes help in cancer prognosis and therapy?","Question",{"text":63,"@type":64},"Mutational landscapes can reflect a cancer’s molecular state and provide markers that support prognosis and therapeutic decisions. Signature analysis refines actionable information beyond single-gene mutation presence.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What role does ERCC2 play in the described bladder cancer study?",{"text":68,"@type":64},"ERCC2 mutation status is validated as an independent predictor of prognosis. The study also uses ERCC2 to stratify cohorts and uncover predictive mutational patterns.",{"name":70,"@type":61,"acceptedAnswer":71},"How are APOBEC-associated mutational signatures affected by ERCC2 mutation status?",{"text":72,"@type":64},"ERCC2-mutated cancers show a higher proportion of SBS2 and a lower proportion of SBS13 compared with ERCC2 wild-type cancers. The genomic distribution of APOBEC mutations also differs, with higher APOBEC mutation rates in accessible early-replicating regions in ERCC2 mutants.","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},331296,1790211556,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,126],{"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":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"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":112,"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":30,"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":112,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","ll  \nOPEN ACCESS  \nPreview  \nGenomic patterns of somatic mutations provide new prognostic, therapeutic, and biological insights in cancer  \nDana Tseitline,1 Yuval Cohen,1 and Sheera Adar1,*  \n1The Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel  \n*Correspondence: [sheera.adar@mail.huji.ac.il](sheera.adar@mail.huji.ac.il)[ ](sheera.adar@mail.huji.ac.il)[https://doi.org/10.1016/j.xgen.2024.100635](https://doi.org/10.1016/j.xgen.2024.100635)  \nThe mutational landscape of an individual’s cancer can inform on its molecular state and be used as prognostic and therapeutic markers. The study by Barbour et al.1 analyzes mutational patterns in bladder cancer samples to uncover new biological insights into the ERCC2 gene function and develop new predictive prognostic tools.  \nThe mutational patterns of cancer genomes reflect the cellular processes that led to mutation accumulation during tumor development and inform about a specific individual’s cancer’s molecular capacities and state. For decades, mutations in known cancer genes have been used to inform clinicians on therapeutic strategies and prognosis. In recent years, wholegenome sequencing of cancer samples has become more affordable and prevalent. These efforts uncover thousands of mutations per cancer genome, but only a handful of these are validated, clinically recognized mutations. The rest are either passenger mutations or mutations of unknown significance. There is still a strong and unmet need for predictive tools that can refine clinically actionable information from these mutations. One approach has been to identify mutational signatures. Mutational signatures are defined not only by the frequencies of the different mutated bases but also by the frequencies of the flanking nucleotides.2 To date, 􀀁 70 single-base substitutions (SBSs), as well as doublet-base substitutions and indel mutational signatures, have been identified and have been associated with specific carcinogenic pathways, treatments, and exposures. For example, signature SBS3 is associated with defects in homologous recombination (HR) repair in breast cancers. SBS3 was first recognized based on its prevalence in BRCA1-and BRCA2-deficient cancers3 but has since been identified in cancers that do not harbor BRCA1/2 mutations, indicating that it  \nmay serve as a better guide for treatments that are indicated for HR-defective cancers such as platinum-based therapies or PARP inhibitors.4 Thus, signature analysis provides a comprehensive functional measurement of the inactivity of a mutagenic pathway complementary to gene-mutation analysis.  \nIn this study, Barbour and colleagues used a comprehensive mutational analysis approach to study bladder cancer (Figure 1) .1 The study was built on two previous observations. First, there is a high prevalence of mutations in the Excision repair cross-complementation group 2 (ERCC2) gene in bladder cancers, which is associated with better prognosis.5 Second, the mutational signatures associated with aberrant activity oftheAPOBEC cytosine deaminase enzyme are enriched in bladder cancers.6 ERCC2 encodes thexeroderma pigmentosum group D (XPD) helicase, a subunit of the transcription factor IIH complex and a key factor in both transcription initiation and nucleotide excision repair (NER) .7,8 In cells, NER is responsible for the removal of bulky and helix-distorting lesions. These include carcinogenic damages induced by ultraviolet radiation in sunlight or by cigarette smoke but also damages induced asa means to kill cancer cells by the chemotherapy cisplatin. Cancer cells defective in ERCC2—and, therefore, NER—respond better to cisplatin therapy.9  \nERCC2 mutant cancers are usually discovered in early tumor stages and generally harbor a higher mutation load.  \nEach of these confounding factors could in itself affect prognosis. Using a large cohort of 1,244 sequenced ","cbCaigWffjGI25Wb","https://ap.wps.com/l/cbCaigWffjGI25Wb","pdf",1779202,"English","# Background: mutational landscapes and clinical need\n## Mutational signatures and APOBEC-related processes\n# Study design and validation in bladder cancer cohorts\n## ERCC2 mutation status as an independent prognostic factor\n# Signature-level findings: SBS2 and SBS13\n## Genomic distribution shifts in ERCC2-mutant tumors\n# Biological interpretation and related DNA repair mechanisms","[{\"question\":\"How do mutational landscapes help in cancer prognosis and therapy?\",\"answer\":\"Mutational landscapes can reflect a cancer’s molecular state and provide markers that support prognosis and therapeutic decisions. Signature analysis refines actionable information beyond single-gene mutation presence.\"},{\"question\":\"What role does ERCC2 play in the described bladder cancer study?\",\"answer\":\"ERCC2 mutation status is validated as an independent predictor of prognosis. The study also uses ERCC2 to stratify cohorts and uncover predictive mutational patterns.\"},{\"question\":\"How are APOBEC-associated mutational signatures affected by ERCC2 mutation status?\",\"answer\":\"ERCC2-mutated cancers show a higher proportion of SBS2 and a lower proportion of SBS13 compared with ERCC2 wild-type cancers. The genomic distribution of APOBEC mutations also differs, with higher APOBEC mutation rates in accessible early-replicating regions in ERCC2 mutants.\"}]","Genomic patterns of somatic mutations provide new prognostic, therapeutic, and biological insights in cancer | PDF",1789992570]