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Mutations are detected in the D-loop, especially the VNTR region, suggesting relevance to replication, transcription, and genome stability. Although overall mutational load is similar, specific changes (m.16168A/G, m.16188G/A, and m.16298A/G) associate with tumour tissues. Heteroplasmy outside the D-loop is not tumour-specific and shows no malignant effects in protein-coding sequences, consistent with a tolerant ROS stress mechanism.",{"@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/defects-in-the-mitochondrial-genome-of-dogs-with-recurrent-tumours/344110/",{"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/defects-in-the-mitochondrial-genome-of-dogs-with-recurrent-tumours/344110.png","ImageObject",300,407,{"name":92,"@type":93},"Clementine","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What sequencing platform was used to analyze mitochondrial DNA in this study?","Question",{"text":112,"@type":113},"Oxford Nanopore Technologies (ONT) was used to perform sequencing of mtDNA from blood and tumour tissues.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which mitochondrial region showed notable mutations associated with tumour progression?",{"text":117,"@type":113},"The D-loop region, particularly the VNTR region, showed mutations that may be important for mitochondrial replication, transcription, and genome stability.",{"name":119,"@type":110,"acceptedAnswer":120},"Do the authors find a difference in overall mutational load between primary and recurrent tumours?",{"text":121,"@type":113},"No. The overall mutational load did not differ between primary and recurrent tumours, although specific mtDNA changes were linked with tumour tissues.","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},344110,1790218727,{"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":8,"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":41},1374391974564,"https://ap-avatar.wpscdn.com/avatar/14000253aa45c000a9e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779874745381141002","Communication  \nDefects in the Mitochondrial Genome of Dogs with Recurrent Tumours  \nKrzysztof Kowal 1, Kaja Ziółkowska-Twarowska 1, Angelika Tkaczyk-Wlizło 1, Ludmiła Grzybowska-Szatkowska 2 and Brygida ´Slaska 1, *  \nCitation: Kowal, K.;  \nZiółkowska-Twarowska, K.;  \nTkaczyk-Wlizło, A.;  \nGrzybowska-Szatkowska, L.; ´Slaska, B. Defects in the Mitochondrial Genome of Dogs with Recurrent Tumours. Int. J. Mol. Sci. 2024, 25, 13414. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms252413414  \nAcademic Editor: Hideko Sone  \nReceived: 29 October 2024  \nRevised: 9 December 2024  \nAccepted: 12 December 2024  \nPublished: 14 December 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Institute of Biological Bases of Animal Production, University of Life Sciences in Lublin, Akademicka 13 St., 20-950 Lublin, Poland; [krzysztof.kowal@up.lublin.pl](krzysztof.kowal@up.lublin.pl) (K.K.); [kaja.ziolkowska@up.lublin.pl](kaja.ziolkowska@up.lublin.pl) (K.Z.-T.); [angelika.tkaczyk@up.lublin.pl](angelika.tkaczyk@up.lublin.pl) (A.T.-W.)  \n2 Department of Radiotherapy, Medical University of Lublin, Chod´zki 7, 20-093 Lublin, Poland; [ludmila.grzybowska-szatkowska@umlub.pl](ludmila.grzybowska-szatkowska@umlub.pl)  \n* [Correspondence: brygida.slaska@up.lublin.pl](Correspondence: brygida.slaska@up.lublin.pl)  \nAbstract: This study presents a comprehensive analysis of mitochondrial DNA (mtDNA) variations in dogs diagnosed with primary and recurrent tumours, employing Oxford Nanopore Technologies (ONT) for sequencing. Our investigation focused on mtDNA extracted from blood and tumour tissues of three dogs, aiming to pinpoint polymorphisms, mutations, and heteroplasmy levels that could influence mitochondrial function in cancer pathogenesis. Notably, we observed the presence of mutations in the D-loop region, especially in the VNTR region, which maybe crucial for mitochondrial replication, transcription, and genome stability, suggesting its potential role in cancer progression. The study is pioneering in its use of long-read sequencing to explore the mutational landscape of mtDNA in canine tumours, revealing that while the overall mutational load did not differ between primary and recurrent tumours, specific changes in m.16168A/G, m.16188G/A, and m.16298A/Gare linked with tumour tissues. Interestingly, the heteroplasmy outside the D-loop region was not specific to tumour tissues and did not provoke any malignant damage in protein-coding sequences, which in turn may be a tolerant effect of the reactive oxygen species (ROS) cellular stress mechanism.  \nKeywords: Oxford Nanopore Sequencing; mtDNA; dog; cancers  \n1. Introduction  \nThe knowledge of molecular disorders occurring in the genetic material of cancer cells is mainly related to nuclear DNA (nDNA) . However, there is a growing number of reports in which mitochondrial DNA (mtDNA) damage is shown tobe important in the neoplastic process [1] . Mitochondria, which have their transcription machineries, play an important role in the cell control of nuclear functions by production of reactive oxygen species (ROS), modulation of calcium levels, and flow control of small molecule metabolites or by regulation of apoptosis [2] . It is, therefore, not surprising that mutations in the mitochondrial genetic material may disrupt cellular homeostasis [3] . Some tissue types give rise to cancers millions of times more often than other tissue types. Although it has been recognized for more than a century, this issue has never been explained [4] .  \nOxford Nanopore Technologies (ONT), with their distinct ability to sequence long strands of DNA and RNA in real-time, have re","cbCaiuiV9gCiI87R","https://ap.wps.com/l/cbCaiuiV9gCiI87R","pdf",841647,12,"English","# Abstract\n# Introduction\n## Mitochondrial DNA in cancer biology\n## Advantages of Oxford Nanopore Technologies for mtDNA analysis\n## D-loop mutations and mechanisms related to ROS and tumour development","[{\"question\":\"What sequencing platform was used to analyze mitochondrial DNA in this study?\",\"answer\":\"Oxford Nanopore Technologies (ONT) was used to perform sequencing of mtDNA from blood and tumour tissues.\"},{\"question\":\"Which mitochondrial region showed notable mutations associated with tumour progression?\",\"answer\":\"The D-loop region, particularly the VNTR region, showed mutations that may be important for mitochondrial replication, transcription, and genome stability.\"},{\"question\":\"Do the authors find a difference in overall mutational load between primary and recurrent tumours?\",\"answer\":\"No. The overall mutational load did not differ between primary and recurrent tumours, although specific mtDNA changes were linked with tumour tissues.\"}]","Defects in the Mitochondrial Genome of Dogs with Recurrent Tumours | PDF",1790053044]