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Despite advances in identifying canine mutational drivers, the contribution of somatic gene fusions in cPAC remains incompletely defined. This study profiles the fusion landscape using RNA-seq from 36 primary tumours and highlights oncogenic, potentially targetable fusions, especially recurrent SDC4::NRG1 events. NRG1 fusions activate HER2 pathway signalling, are mutually exclusive with HER2 alterations, and correlate with overexpression of HER2-related genes, supporting fusion-driven disease progression. The work also identifies novel fusions disrupting the PTEN axis, generating truncated PTEN and related protein domains.",{"@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/genomic-landscape-analysis-of-canine-pulmonary-adenocarcinoma-reveals-candidate-targetable-gene-fusions/352902/",{"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/genomic-landscape-analysis-of-canine-pulmonary-adenocarcinoma-reveals-candidate-targetable-gene-fusions/352902.png","ImageObject",300,407,{"name":92,"@type":93},"Chumphorn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","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 is the main aim of the study on canine pulmonary adenocarcinoma?","Question",{"text":112,"@type":113},"To investigate the somatic gene fusion landscape in canine pulmonary adenocarcinoma and identify oncogenic fusions with therapeutic potential.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which fusion events were notably identified in a subset of cPAC tumours?",{"text":117,"@type":113},"NRG1 fusions, including recurrent SDC4::NRG1 events, were found in a subset of tumours.",{"name":119,"@type":110,"acceptedAnswer":120},"How do NRG1 fusions relate to HER2 signalling and HER2 gene alterations?",{"text":121,"@type":113},"NRG1 fusions are known to activate HER2 signalling and are mutually exclusive with HER2 gene alterations, suggesting convergence on the same pathway.","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},352902,1790523111,{"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":145},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","Veterinary and Comparative Oncology  \nORIGINAL ARTICLE  OPEN ACCESS   \nGenomic Landscape Analysis of Canine Pulmonary Adenocarcinoma Reveals Candidate Targetable Gene Fusions  \nSharadha Sakthikumar1  | William P. D. Hendricks1  | David Rainford1 | William Selleck1 | Natalia Briones1 |  \nChristopher Coggins1 | Natalie Quan1 | Victoria Zismann1 | Gwendolen Lorch2  | Aleksandar Sekulic1 | Jeffrey M. Trent1 1Translational Genomics Research Institute, Phoenix, Arizona, USA | 2MedVet, Columbus, Ohio, USA  \nCorrespondence: Aleksandar Sekulic ([asekulic@tgen.org](asekulic@tgen.org)) | Jeffrey M. Trent ([jtrent@tgen.org](jtrent@tgen.org))  \nReceived: 26 March 2025 | Revised: 24 September 2025 | Accepted: 23 December 2025  \nKeywords: cancer | cPAC | dogs | fusions | NSCLC | pulmonary adenocarcinoma  \nABSTRACT  \nSpontaneously occurring primary canine pulmonary adenocarcinoma (cPAC) exhibits clinicopathological and molecular similarities to never-smoker human lung cancers. Shared genomic alterations, including point mutations, indel mutations and copy number changes particularly in HER2 signalling, are significant therapeutic targets, especially for HER2 and tyrosine kinase inhibitors. Whilst progress has been made in identifying mutational drivers in canine cancers, the role of somatic gene fusionsin cPAC remains poorly understood, despite their importance in other cancers as drivers and therapeutic targets. This study investigates the fusion landscape in cPAC by analysing RNA-seq data from a cohort of 36 primary tumour samples and reportsoncogenic fusions with therapeutic potential. Notably, NRG1 fusions were identified in a subset of tumours, including recurrent SDC4::NRG1 events, potentially playing key roles in disease progression. NRG1 fusions, known to activate HER2 signalling, are mutually exclusive with HER2 gene alterations, indicating convergence on the same pathway. Tumours with SDC4::NRG1 fusions also overexpress HER2 pathway-related genes, reinforcing NRG1-driven activation. Similar fusions occur in never-smoker human non-small cell adenocarcinoma lacking other common drivers, underscoring their therapeutic importance. These findings highlight NRG1 fusions as critical contributors to cPAC tumorigenesis and warrant further clinical and comparative investigation. Additionally, novel fusions disrupting the PTEN axis were identified, leading to truncated PTEN and associated protein domains. These disruptions could impair tumour-suppressive pathways, presenting additional therapeutic targets. This research emphasises the broader relevance of fusion-driven mechanisms in cPAC tumorigenesis, advancing the understanding of both canine and human lung cancers for clinical and comparative studies.  \n1 | Introduction  \nLung cancer is one of the most prevalent cancers in humans [1], with non-small cell lung cancer (hNSCLC) being the most common type, accounting for 85% of all cases [1] . In dogs, lung cancer is comparatively rare, making up only 1% of all canine cancers [2] . The canine equivalent of hNSCLCis canine pulmonary adenocarcinoma (cPAC), which has an  \nannual incidence rate of 15 per 100 000 dogs in the United Kingdom [3] . Although large-scale epidemiological studies evaluating breed predisposition to cPAC have not been conducted, one study of 88 dogs reported that mixed breeds were more frequently represented (25%) than purebreds, including Labrador Retrievers (21%) and Bichon Frise (5%) [4] . Despite its rarity, cPAC shares similar clinical features, histopathological characteristics and oncogenic mechanisms with human  \n\n| Sharadha Sakthikumar and William P. D. Hendricks share joint first authorship. |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.\u003Cbr>© 2026 The Author(s). Veterinary and Comparative Oncology published by John Wiley & Sons Ltd. |\n\nVeterinary and ","cbCailOW08LYBG7L","https://ap.wps.com/l/cbCailOW08LYBG7L","pdf",1157880,14,"English","# Abstract\n# Introduction","[{\"question\":\"What is the main aim of the study on canine pulmonary adenocarcinoma?\",\"answer\":\"To investigate the somatic gene fusion landscape in canine pulmonary adenocarcinoma and identify oncogenic fusions with therapeutic potential.\"},{\"question\":\"Which fusion events were notably identified in a subset of cPAC tumours?\",\"answer\":\"NRG1 fusions, including recurrent SDC4::NRG1 events, were found in a subset of tumours.\"},{\"question\":\"How do NRG1 fusions relate to HER2 signalling and HER2 gene alterations?\",\"answer\":\"NRG1 fusions are known to activate HER2 signalling and are mutually exclusive with HER2 gene alterations, suggesting convergence on the same pathway.\"}]","Genomic Landscape Analysis of Canine Pulmonary Adenocarcinoma Reveals Candidate Targetable Gene Fusions | PDF",1790101941,35]