[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-406579-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-406579-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","pdj-amplicon-in-triple-negative-breast-cancer","PDJ amplicon in triple negative breast cancer","","Amplification of chromosome 9p24.1 targeting PD-L1, PD-L2, and JAK2 (PDJ amplicon) occurs in subsets of triple negative breast cancers (TNBC) and is linked to poor outcomes, yet its prevalence differs across studies. A cohort of 360 TNBC samples was analyzed using a 3-color FISH assay, alongside correlative tests of tumor-infiltrating lymphocytes and intratumor copy number. Matched pre- and post-neoadjuvant biopsies (n=6) assessed therapy effects on PDJ status.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/pdj-amplicon-in-triple-negative-breast-cancer/406579/",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/pdj-amplicon-in-triple-negative-breast-cancer/406579.png","ImageObject",300,407,{"name":42,"@type":43},"WPS_1790064749","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the PDJ amplicon and why is it relevant in TNBC?","Question",{"text":63,"@type":64},"The PDJ amplicon is a chromosome 9p24.1 amplification targeting PD-L1, PD-L2, and JAK2. It is present in subsets of TNBC and is associated with poor clinical outcomes.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was PDJ amplification determined in the study?",{"text":68,"@type":64},"PDJ status was assessed using a 3-color fluorescence in situ hybridization (FISH) assay targeting 9p24.1 (PDJ), 9q24.3, and 9q34.1. Samples were called amplified when specific signal copy number and ratio thresholds were met.",{"name":70,"@type":61,"acceptedAnswer":71},"How did neoadjuvant treatment affect PDJ status?",{"text":72,"@type":64},"Matched pre- and post-neoadjuvant biopsies were available for a subset of patients (n=6) to evaluate how therapy changed PDJ status.","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},406579,1790922694,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,109,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"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":106,"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":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},3985747859154,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nPDJ amplicon in triple negative breast cancer  \nAlexander S. Roesler1,2, Smriti Malasi1, Lori Koslosky3, Peter Hartmayer3, Tammey J. Naab4, Jodi M. Carter 5,6, David Zahrieh7, David Hillman7, Roberto A. Leon‑Ferre8, Fergus J. Couch 5, Matthew P. Goetz8, Karen S. Anderson9,10, Barbara A. Pockaj11 & Michael T. Barrett1,12*  \nAmplification of chromosome 9p24.1 targeting PD-L1, PD-L2, and JAK2 (PDJ amplicon) is present in subsets of triple negative breast cancers (TNBCs) and is associated with poor clinical outcomes. However, the prevalence of PDJ+ TNBCs varies extensively across studies applying different methods for interrogating samples of interest. To rigorously assess the prevalence of PDJ amplicons in  \nTNBC, its prognostic value and whether it is enriched by chemotherapy, we interrogated 360 TNBC samples including 74 surgical resections from patients treated in the neoadjuvant setting, and tissue microarrays (TMAs) with 31 cases from African American women and 255 resected non‑metastatic cases, with a 3 color fluorescence in situ hybridization (FISH) assay targeting the 9p24.1 PDJ amplicon, 9q24.3, and 9q34.1 . Samples with mean PDJ signal of > 4.5 copies, and ratios of PDJ/9q24 ≥ 2 and/or  \nPDJ/9q34.1 ≥ 2 were called amplified (PDJ+) . Correlative analyses included the association of tumor infiltrating lymphocytes (TILs) with PDJ amplicons inTNBCs. In addition, we investigated intratumor copy number of PDJ amplicons in PDJ+ and PDJ− TNBCs. Matched pre‑ and post‑neoadjuvant treatment biopsies were available from patients (n = 6) to evaluate the effects of therapy on PDJ status. Our study provides a rigorous analysis of the prevalence, distribution, and clinical correlatives of the PDJ amplicon inTNBC.  \nThere is an emerging recognition of immune checkpoints in the pathogenesis of solid tumors 1. Immune checkpoints are distinct inhibitory pathways that normally serve to regulate T cell activation and function. These pathways include activation of the programmed cell death protein one (PD-1) receptor by its ligands PD-L1 and PD-L2. Increased expression of PD-1 and its ligands have been reported in human tumors suggesting that tumors may exploit the PD-1 mediated checkpoint to evade immune surveillance2–5, augmented by somatic mutational burden6–8. Accelerated approval for advanced TNBC was granted to the PD-L1 inhibitor atezolizumab in 03/2019 based on the IMpassion130 trial, and to the PD-1 inhibitor pembrolizumab in 11/2020 based on KEYNOTE-355 . Pembrolizumab also has an approved indication for high-risk early-stage TNBC based on KEYNOTE-522 . However, the follow-up trial of atezolizumab in advanced TNBC (IMpassion131) failed to demonstrate a survival benefit, such that the manufacturer withdrew its TNBC indication in 08/2021 . Nonetheless, evaluation of pembrolizumab in breast cancer is ongoing, with some promising clinical activity in PD-L1 positive estrogen receptor (ER) + breast cancer based on KEYNOTE-028 .  \nExploratory biomarker analyses suggest an association of clinical response to immune checkpoint inhibitors (ICIs) with the presence of stromal tumor-infiltrating lymphocytes (TILs), CD8 + T cells, and PD-L1 expression, but these associations have yet to demonstrate clinical utility9. An emerging picture suggests that tumor specific genomic lesions, either individually or in combination, are associated with immune checkpoint activation and the extent and duration of responses for patients to immunotherapy. These lesions include loss of tumor suppressor genes (PTEN), the activation of oncogenic drivers (EGFR, KRAS, and PIK3CA), BRCA mutant and BRCA-like homologous recombination deficient (HRD) genomes, and high mutation burdens including those associated with microsatellite instability (MSI), chromosomal instability (CIN) and aneuploidy10–16. Immunohistochemistry  \n1Department of Research, Mayo Clinic in Arizona, Scottsdale, AZ, USA. 2S","cbCaihN6hfhMd2QH","https://ap.wps.com/l/cbCaihN6hfhMd2QH","pdf",1389032,11,"English","# Background and clinical rationale\n## Immune checkpoint biology in solid tumors\n# Study design and methods\n## Cohort composition and FISH criteria\n## Correlative and copy-number analyses\n## Neoadjuvant biopsy evaluation\n# Biological context and biomarkers\n## Stromal TILs, CD8+ cells, and PD-L1\n## Genomic lesions linked to checkpoint activation\n# Genomic versus protein-based assay considerations\n## IHC thresholds and genomic amplification scoring\n# 9p24.1 locus organization and prior findings","[{\"question\":\"What is the PDJ amplicon and why is it relevant in TNBC?\",\"answer\":\"The PDJ amplicon is a chromosome 9p24.1 amplification targeting PD-L1, PD-L2, and JAK2. It is present in subsets of TNBC and is associated with poor clinical outcomes.\"},{\"question\":\"How was PDJ amplification determined in the study?\",\"answer\":\"PDJ status was assessed using a 3-color fluorescence in situ hybridization (FISH) assay targeting 9p24.1 (PDJ), 9q24.3, and 9q34.1. Samples were called amplified when specific signal copy number and ratio thresholds were met.\"},{\"question\":\"How did neoadjuvant treatment affect PDJ status?\",\"answer\":\"Matched pre- and post-neoadjuvant biopsies were available for a subset of patients (n=6) to evaluate how therapy changed PDJ status.\"}]","PDJ amplicon in triple negative breast cancer | PDF",1790566549,28]