[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-356250-105":3,"detail-sidebar-cat-0-en-105":79,"doc-detail-356250-en":129},{"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":72,"head_meta":74,"extra_data":76,"updated_unix":78},105,"en","whole-genome-sequencing-approach-to-assess-homologous-recombination-deficiency-in-a-pan-cancer-cohort","Whole genome sequencing approach to assess homologous recombination deficiency in a pan-cancer cohort","","Homologous recombination deficiency (HRD) influences cancer treatment decisions, especially for effective use of PARP inhibitors, yet inconsistent results across HRD assays complicate identifying patients most likely to benefit. A study applies a whole-genome sequencing HRD classifier to 580 tumor/normal paired samples, correlating the inferred HRD phenotype with BRCA1/2 and other homologous recombination repair gene variants. Results describe HRD across multiple cancer types and highlight cases beyond BRCA1/2 mutations, with evidence of improved concordance with treatment response for the genome-wide approach.",{"@graph":14,"@context":71},[15,34,54],{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/whole-genome-sequencing-approach-to-assess-homologous-recombination-deficiency-in-a-pan-cancer-cohort/356250/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":48,"encodingFormat":47,"isAccessibleForFree":49,"interactionStatistic":50},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/whole-genome-sequencing-approach-to-assess-homologous-recombination-deficiency-in-a-pan-cancer-cohort/356250.png","ImageObject",300,407,{"name":42,"@type":43},"Himbo","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23",true,{"@type":51,"interactionType":52,"userInteractionCount":26},"InteractionCounter",{"@type":53},"ViewAction",{"@type":55,"mainEntity":56},"FAQPage",[57,63,67],{"name":58,"@type":59,"acceptedAnswer":60},"Why is homologous recombination deficiency (HRD) clinically important?","Question",{"text":61,"@type":62},"HRD affects how cancers respond to therapies such as PARP inhibitors. It reflects a cancer cell’s inability to repair certain DNA damage types, creating vulnerabilities to drugs targeting DNA repair.","Answer",{"name":64,"@type":59,"acceptedAnswer":65},"How does the study evaluate HRD using whole genome sequencing?",{"text":66,"@type":62},"It uses a whole genome sequencing HRD classifier based on genome-wide HRD signatures and analyzes 580 tumor/normal paired samples. The HRD phenotype is then correlated with genomic variants in BRCA1/2 and other HRR genes.",{"name":68,"@type":59,"acceptedAnswer":69},"Are HRD cases limited to BRCA1/2 mutations?",{"text":70,"@type":62},"No. The results show HRD cases occur across several cancer types and that a substantial fraction of HRD cases are BRCA1/2 wild-type, indicating HRD can arise from other genomic mechanisms.","https://schema.org",{"og:url":32,"og:type":73,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":75,"canonical":32},"index,follow",{"doc_id":77,"site_id":7},356250,1790179682,{"code":4,"msg":80,"data":81},"success",[82,86,90,94,99,104,108,113,118,121,125],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":83,"show_sort_weight":84,"slug":85},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":87,"show_sort_weight":88,"slug":89},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":91,"show_sort_weight":92,"slug":93},"Exam",70,"exam",{"id":95,"doc_module":4,"doc_module_name":25,"category_name":96,"show_sort_weight":97,"slug":98},5,"Comic",60,"comic",{"id":100,"doc_module":4,"doc_module_name":25,"category_name":101,"show_sort_weight":102,"slug":103},6,"Technology",50,"technology",{"id":105,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":106,"slug":107},7,40,"healthcare",{"id":109,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},8,"Research & Report",30,"research-report",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},9,"Religion & Spirituality",20,"religion-spirituality",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":119,"show_sort_weight":116,"slug":120},"World Cup","world-cup",{"id":122,"doc_module":4,"doc_module_name":25,"category_name":123,"show_sort_weight":122,"slug":124},10,"Lifestyle","lifestyle",{"id":126,"doc_module":4,"doc_module_name":25,"category_name":127,"show_sort_weight":95,"slug":128},19,"General","general",{"code":4,"msg":80,"data":130},{"doc_id":77,"user_id":131,"nickname":42,"user_avatar":132,"doc_module":4,"category_id":105,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":26,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":122,"language":138,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":12,"update_tm":142,"read_time":143},687197100911,"https://ap-avatar.wpscdn.com/avatar/a000239b6f1da00475?x-image-process=image/resize,m_fixed,w_180,h_180&k=1785132997149421697","A Nature Portfolio journal  \n[https://doi.org/10.1038/s43856-025-01308-5](https://doi.org/10.1038/s43856-025-01308-5)  \nWhole genome sequencing approach to assess homologous recombination deficiency in a pan-cancer cohort  \n Check for updates  \n\n| MajdAl Assaad 1,2,7, Kevin Hadi3,7, Max F. Levine 3,7, Daniela Guevara 2,4, Minal Patel3,\u003Cbr>Marvel Tranquille 2, Abigail King 2, John Otilano2, Alissa Semaan2, Gunes Gundem3,\u003Cbr>Juan S. Medina-Martínez3, Michael Sigouros 2, Jyothi Manohar2, Hui-Hsuan Kuo 2, David C. Wilkes 2, Eleni Andreopoulou2,4, Eloise Chapman-Davis2,4, Scott T. Tagawa 2,4, Andrea Sboner 1,2,\u003Cbr>Allyson J. Ocean2,4, Manish A. Shah 2,4, Elli Papaemmanuil3, Cora N. Sternberg 2,4, Kevin Holcomb2,4, David M. Nanus2,4, Olivier Elemento 2,5,6 & Juan Miguel Mosquera 1,2  |  |  |\n| --- | --- | --- |\n| Abstract |  | Plain language summary |\n| Background Homologous recombination deficiency (HRD) impacts cancer treatment strategies, particularly effective utilization of PARP inhibitors. However, the variability of different HRD assays has hampered the selection of oncology patients who may benefit from these therapies. Our study aims to use the whole genome landscape to better define HRD in a pan-cancer cohort.\u003Cbr>Methods We employed a whole genome sequencing HRD classifier that includes genomewide signatures associated with HRD to analyze 580 tumor/normal paired samples. The HRD phenotype was correlated with genomic variants in BRCA1/2 and other homologous recombination repair genes.\u003Cbr>Results In this paper we show that the HRD phenotype is identified in various cancers including breast (21%), pancreaticobiliary (20%), gynecological (17%), prostate (9%), upper gastrointestinal (GI) (2%), and other cancers (1%) . HRD cases are not confined to BRCA1/2 mutations; 24% of HRD cases are BRCA1/2 wild-type. A diverse range of gene alterations involved in HRDare elucidated, including biallelic mutations inFANCF,XRCC2, andFANCC, and deleterious structural variants. In a subset of cases, the whole genome sequencingbased classifier offers more insights and a better correlation to treatment response when compared to other assays.\u003Cbr>Conclusions Although HRD is a biomarker used to determine which cancer patients would benefit from PARP inhibitors, a lack of harmonization of tests to determine HRD status makes it challenging to interpret their results. Our study highlights the use of comprehensive whole genome sequencing analysis to better predict HRD and elucidates genomic mechanisms associated with this phenotype. |  | Homologous recombination deficiency is a condition in which a cancer cell cannot repair certain types of DNA damage. It causes genetic instability and is often due to changes in parts of the DNA called genes, such as BRCA1 and BRCA2 . Cancers with this deficiency can be more readily killed by certain drugs that prevent DNA repair. Some of these drugs are approved for the treatment of several types of cancer, including ovarian, breast, pancreatic, and prostate cancers. To better identify tumors with this deficiency, we characterize the whole genome of cancer samples. We find that a comprehensive analysis of the entire genome improves the detection of homologous recombination deficiency. This type of analysis may provide a more accurate way to guide treatment decisions for people with cancer. |\n| BRCA1 and BRCA2 (BRCA1/2)playa significant role in an error-free DNA damage repair pathway known as homologous recombination repair (HRR)1. This pathway corrects DNA double-strand breaks (DSBs) and interstrand cross-links1,2. Somatic or germline mutations in BRCA1/2 | (BRCAmut)lead to homologous recombination deficiency(HRD)and have long been associated with breast, ovarian, pancreatic, and prostate cancers3,4. Poly (ADP-ribose) polymerase inhibitors (PARPi) have been developed to treat cancers associated with mutations in BRCA1/2 and other HRR genes |  |\n\n1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, US","cbCais0HbqLduEvD","https://ap.wps.com/l/cbCais0HbqLduEvD","pdf",1598849,"English","# Abstract / Plain language summary\n## Background\n## Methods\n## Results\n## Conclusions\n# Scientific background\n## Role of BRCA1/2 and HRR\n## Current clinical HRD assessment methods\n## HRD-associated DNA damage signatures","[{\"question\":\"Why is homologous recombination deficiency (HRD) clinically important?\",\"answer\":\"HRD affects how cancers respond to therapies such as PARP inhibitors. It reflects a cancer cell’s inability to repair certain DNA damage types, creating vulnerabilities to drugs targeting DNA repair.\"},{\"question\":\"How does the study evaluate HRD using whole genome sequencing?\",\"answer\":\"It uses a whole genome sequencing HRD classifier based on genome-wide HRD signatures and analyzes 580 tumor/normal paired samples. The HRD phenotype is then correlated with genomic variants in BRCA1/2 and other HRR genes.\"},{\"question\":\"Are HRD cases limited to BRCA1/2 mutations?\",\"answer\":\"No. The results show HRD cases occur across several cancer types and that a substantial fraction of HRD cases are BRCA1/2 wild-type, indicating HRD can arise from other genomic mechanisms.\"}]","Whole genome sequencing approach to assess homologous recombination deficiency in a pan-cancer cohort | PDF",1790124255,25]