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This study identifies chromosome 8p–specific vulnerabilities for tumors with chromosome 8p deletions using integrative analysis of TCGA, DepMap, and cancer cell line data. SLC25A28/MFRN2 is pinpointed as vulnerable, with sensitivity determined by the expression of its paralog SLC25A37/MFRN1 on chromosome 8p. Loss of the paralogs disrupts mitochondrial iron-transport function, reduces iron-sulfur cluster proteins, causes DNA damage, and triggers cell death, suppressing growth and enabling tumor eradication in mouse xenografts.",{"@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/mitoferrin2-is-a-synthetic-lethal-target-for-chromosome-8p-deleted-cancers/330840/",{"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/mitoferrin2-is-a-synthetic-lethal-target-for-chromosome-8p-deleted-cancers/330840.png","ImageObject",300,407,{"name":92,"@type":93},"Violet","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What vulnerability was identified for chromosome 8p deleted tumors?","Question",{"text":112,"@type":113},"SLC25A28, also known as Mitoferrin2 (MFRN2), was identified as a specific vulnerability for tumors harboring chromosome 8p deletions.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is sensitivity to MFRN2 loss determined?",{"text":117,"@type":113},"Vulnerability to MFRN2 loss is dictated by expression of its paralog SLC25A37 (MFRN1), which is located on chromosome 8p.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic evidence supports targeting MFRN2?",{"text":121,"@type":113},"In MFRN1-deficient tumors, MFRN2 depletion impaired growth and led to tumor eradication in preclinical mouse xenograft experiments, indicating therapeutic potential.","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},330840,1790019750,{"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":34,"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,"preview_page_count":4},4398048950312,"https://ap-avatar.wpscdn.com/avatar/400002538284de19e3c?_k=1778320343897328908","Krieg et al. Genome Medicine (2024) 16:83 [https://doi.org/10.1186/s13073-024-01357-w](https://doi.org/10.1186/s13073-024-01357-w)  \nGenome Medicine  \n RESEARCH Open Access  \nMitoferrin2 is a synthetic lethal target for chromosome 8p deleted cancers  \nStephan Krieg1, Thomas Rohde2, Tobias Rausch3, Luise Butthof1, Lena Wendler‑Link1, Christoph Eckert 1, Kai Breuhahn4, Bruno Galy5, Jan Korbel3, Maximilian Billmann2*, Marco Breinig1* and  \nDarjus F. Tschaharganeh 1*  \nAbstract  \nBackground Somatic copy number alterations are a hallmark of cancer that offer unique opportunities for therapeu‑ tic exploitation. Here, we focused on the identification of specific vulnerabilities for tumors harboring chromosome 8p deletions.  \nMethods We developed and applied an integrative analysis of The Cancer Genome Atlas (TCGA), the Cancer Dependency Map (DepMap), and the Cancer Cell Line Encyclopedia to identify chromosome 8p‑specific vulnerabili‑ ties. We employ orthogonal gene targeting strategies, both in vitro and in vivo, including short hairpin RNA‑mediated gene knockdown and CRISPR/Cas9‑mediated gene knockout to validate vulnerabilities.  \nResults We identified SLC25A28 (also known as MFRN2), as a specific vulnerability for tumors harboring chromo‑ some 8p deletions. We demonstrate that vulnerability towards MFRN2 loss is dictated by the expression of its paralog, SLC25A37 (also known as MFRN1), which resides on chromosome 8p. In line with their function as mitochondrial iron transporters, MFRN1/2 paralog protein deficiency profoundly impaired mitochondrial respiration, induced global depletion of iron‑sulfur cluster proteins, and resulted in DNA‑damage and cell death. MFRN2 depletion in MFRN1‑ deficient tumors led to impaired growth and even tumor eradication in preclinical mouse xenograft experiments, highlighting its therapeutic potential.  \nConclusions Our data reveal MFRN2 as a therapeutic target of chromosome 8p deleted cancers and nominate MFNR1 as the complimentary biomarker for MFRN2‑directed therapies.  \nKeywords Synthetic lethality, Chromosome 8p deletion, SCNAs, MFRN1/2 paralog buffering  \n*Correspondence:  \nMaximilian Billmann [maximilian.billmann@gmail.com](maximilian.billmann@gmail.com)[ ](maximilian.billmann@gmail.com)Marco Breinig [marco.breinig@gmail.com](marco.breinig@gmail.com)[ ](marco.breinig@gmail.com)Darjus F. Tschaharganeh[d.tschaharganeh@dkfz.de](d.tschaharganeh@dkfz.de)  \n1 Helmholtz‑University Group“Cell Plasticity and Epigenetic Remodeling”, German Cancer Research Center (DKFZ), Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany  \n2 Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany  \n3 European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany  \n4 Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany  \n5 Division of Virus‑Associated Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creativ","cbCailjFzaUAknDB","https://ap.wps.com/l/cbCailjFzaUAknDB","pdf",2902894,21,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Main Text\n## Synthetic lethality and SCNAs","[{\"question\":\"What vulnerability was identified for chromosome 8p deleted tumors?\",\"answer\":\"SLC25A28, also known as Mitoferrin2 (MFRN2), was identified as a specific vulnerability for tumors harboring chromosome 8p deletions.\"},{\"question\":\"How is sensitivity to MFRN2 loss determined?\",\"answer\":\"Vulnerability to MFRN2 loss is dictated by expression of its paralog SLC25A37 (MFRN1), which is located on chromosome 8p.\"},{\"question\":\"What therapeutic evidence supports targeting MFRN2?\",\"answer\":\"In MFRN1-deficient tumors, MFRN2 depletion impaired growth and led to tumor eradication in preclinical mouse xenograft experiments, indicating therapeutic potential.\"}]","Mitoferrin2 is a synthetic lethal target for chromosome 8p deleted cancers | PDF",1789990430,53]