[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-344704-105":59,"doc-detail-344704-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","mutational-landscape-of-normal-breast-tissues-adjacent-to-invasive-breast-cancer-article","Mutational landscape of normal breast tissues adjacent to invasive breast cancer - Article","","Suwalska and colleagues investigate how normal breast tissues adjacent to invasive breast cancer acquire cancer-relevant genomic alterations. Using matched samples from peripheral blood, cancer-adjacent normal breast, and tumors in two cohorts, they compare gene and pathway mutation profiles and single-base substitution signatures. The work shows acquired somatic mutations in cancer-adjacent tissue that persist in tumors, with many variants shared within individuals, highlighting strong germline influence on malignant transformation.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mutational-landscape-of-normal-breast-tissues-adjacent-to-invasive-breast-cancer-article/344704/",{"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/mutational-landscape-of-normal-breast-tissues-adjacent-to-invasive-breast-cancer-article/344704.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does the study focus on regarding tissues next to breast cancer?","Question",{"text":112,"@type":113},"The study analyzes cancer-relevant mutations in normal breast tissues adjacent to invasive breast cancer, including how acquired somatic changes relate to tumors.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do the authors assess genetic alterations across the samples?",{"text":117,"@type":113},"They compare gene- and pathway-level mutation profiles and single-base substitution (SBS) signatures across matched peripheral blood, cancer-adjacent normal breast, and breast cancer samples in two independent cohorts.",{"name":119,"@type":110,"acceptedAnswer":120},"What role do germline polymorphisms play in the findings?",{"text":121,"@type":113},"The findings indicate substantial germline contribution: many variants in cancer-relevant pathways are shared across tissue types from the same individual, supporting a collective impact model of cancer risk.","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},344704,1790211951,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"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":36},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","Article  \nMutational landscape of normal breast tissues adjacent to invasive breast cancer  \nAuthors  \nAleksandra Suwalska, Mariya Rozenblit, Malini Harigopal, ..., Jeffrey P. Townsend, Michal Marczyk, Lajos Pusztai  \nCorrespondence  \n[aleksandra.suwalska@polsl.pl](aleksandra.suwalska@polsl.pl) (A.S.),  \n[lajos.pusztai@yale.edu](lajos.pusztai@yale.edu) (L.P.)  \nIn brief  \nSuwalska et al. show that canceradjacent normal breast tissues share genomic alterations with cancer, and many changes in cancer-relevant genes arise from specific combinations of germline polymorphisms. This supports gradual mutation-driven malignant transformation of normal cells and suggests context-dependent cooncogenic function for common and rare germline polymorphisms.  \n• Cancer-adjacent normal breast tissues carry many of the same mutations found in cancer  \n• A patient-specific pattern of pathway-level mutations indicates phenotypic convergence  \n• Vast gHFIs not linked to cancer risk suggest contextdependent biological effect  \nSuwalska et al., 2026, Cell Reports Medicine 7, 102543  \nJanuary 20, 2026 © 2025 The Author(s) . Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.xcrm.2025.102543](https://doi.org/10.1016/j.xcrm.2025.102543)  \nll  \nll  \nOPEN ACCESS  \nArticle  \nMutational landscape of normal breast tissues adjacent to invasive breast cancer  \nAleksandra Suwalska,1,5,6,* Mariya Rozenblit,2,5 Malini Harigopal,2,3 Jiawei Dai,2 Meng Liu,4 Jeffrey P. Townsend,4 Michal Marczyk,1,2 and Lajos Pusztai2,*  \n1Department of Data Science and Engineering, Silesian University of Technology, 44-100 Gliwice, Poland  \n2Yale Cancer Center, Yale University, New Haven, CT 06510, USA  \n3Department of Pathology, Mount Sinai Hospital, New York City, NY 10029, USA  \n4Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510, USA  \n5These authors contributed equally  \n6Lead contact  \n*Correspondence: [aleksandra.suwalska@polsl.pl](aleksandra.suwalska@polsl.pl) (A.S.), [lajos.pusztai@yale.edu](lajos.pusztai@yale.edu) (L. P.) [https://doi.org/10.1016/j.xcrm.2025.102543](https://doi.org/10.1016/j.xcrm.2025.102543)  \nSUMMARY  \nIndividuals with a history of breast cancer are at increased risk of developing a new breast cancer during their lifetime. Rare but high-impact somatic mutations in normal breast tissues may contribute to malignant transformation. We analyze mutations in cancer-relevant pathways across matched samples of peripheral blood, cancer-adjacent normal breast, and breast cancer from patients diagnosed before 50 years of age who carry no germline mutations in cancer-predisposing genes. Gene- and pathway-level mutation profiles and single-base substitution (SBS) signatures are compared between tissue types in two independent cohorts (Yale, n = 24; TCGA, n = 17) . Cancer-adjacent normal breast tissue contains multiple acquired somatic mutations that persist in tumors. Most variants are shared across tissue types from the same individual, indicating strong germline influence. The substantial germline contribution to alterations through common and rare polymorphisms in cancer hallmark pathways supports a model of cancer risk based on the collective impact of variants in cancer-related genes.  \nINTRODUCTION  \nBreast cancer has emerged as the predominant cancer diagnosis and primary cause of cancer-related mortality in women in 107 out of 184 countries based on recent World Health Organization estimates.1 It is a complex and multifactorial disease with a pathophysiology that remains incompletely understood. The development of breast cancer is believed to involve a combination of environmental, lifestyle, hormonal, and genetic factors. Advancing age and being female are the most common risk factors associated with the disease2; however, the incidence of early-onset breast cancer, diagnosed in young women before the age of 50 years, is increasing.3 Early-onset breast cancer is characterized by larger tumor size, more frequent lymph node i","cbCaijJ8Mcc8bIRJ","https://ap.wps.com/l/cbCaijJ8Mcc8bIRJ","pdf",6057603,16,"English","# Summary\n# Introduction\n## Breast cancer risk factors and early-onset disease\n## Genomic context-dependent effects and hallmark pathways\n## Prior evidence of epigenetic and genetic field defects","[{\"question\":\"What does the study focus on regarding tissues next to breast cancer?\",\"answer\":\"The study analyzes cancer-relevant mutations in normal breast tissues adjacent to invasive breast cancer, including how acquired somatic changes relate to tumors.\"},{\"question\":\"How do the authors assess genetic alterations across the samples?\",\"answer\":\"They compare gene- and pathway-level mutation profiles and single-base substitution (SBS) signatures across matched peripheral blood, cancer-adjacent normal breast, and breast cancer samples in two independent cohorts.\"},{\"question\":\"What role do germline polymorphisms play in the findings?\",\"answer\":\"The findings indicate substantial germline contribution: many variants in cancer-relevant pathways are shared across tissue types from the same individual, supporting a collective impact model of cancer risk.\"}]","Mutational landscape of normal breast tissues adjacent to invasive breast cancer - Article | PDF",1790054994]