[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-372745-105":59,"doc-detail-372745-en":134},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":127,"head_meta":129,"extra_data":131,"updated_unix":133},105,"en","novel-maml2-fusions-in-human-malignancy","Novel MAML2 Fusions in Human Malignancy","","Research identifies oncogenic gene fusions involving the MAML2 transcriptional activation domain across diverse human malignancies, expanding beyond established partners. Tumor DNA/RNA sequencing from Caris Life Sciences enabled RNA-based detection and filtering for in-frame, C-terminal MAML2 TAD–containing fusions and quantification of fusion burden. Among 180,124 samples, 143 harbored MAML2 fusions, with mostly known events plus novel partners. Novel fusions showed lower expression, higher fusion burden, and more frequent TP53 co-mutations, while ATXN3::MAML2 differed, suggesting distinct biology and potential pathogenic relevance.",{"@graph":69,"@context":126},[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":10,"@type":76,"position":81},"https://docshare.wps.com/document/story-novel/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/novel-maml2-fusions-in-human-malignancy/372745/",{"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/novel-maml2-fusions-in-human-malignancy/372745.png","ImageObject",300,407,{"name":92,"@type":93},"Blitz","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What is MAML2 and why are its fusions important in cancers?","Question",{"text":112,"@type":113},"MAML2 is a Mastermind family member that regulates NOTCH signaling by activating downstream transcription. Fusions retaining its transactivating domain can drive aberrant gene transcription and influence malignancy development.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were novel MAML2 fusions identified in the study?",{"text":117,"@type":113},"Tumor DNA and RNA sequencing from Caris Life Sciences was used to identify MAML2 fusions from RNA transcripts. Fusions were filtered to include only known pathogenic events or recurrent in-frame fusions containing a C-terminal MAML2 TAD.",{"name":119,"@type":110,"acceptedAnswer":120},"What distinguishes the novel MAML2 fusions from the known ones?",{"text":121,"@type":113},"Compared with known fusions, novel fusions generally had lower expression, higher fusion burden, more frequent TP53 co-mutations, and no clear association with tissue of origin.",{"name":123,"@type":110,"acceptedAnswer":124},"Why is ATXN3::MAML2 considered potentially pathogenic?",{"text":125,"@type":113},"Excluding ATXN3::MAML2, novel partners were typically near MAML2 and likely arose from copy-number changes. In contrast, ATXN3::MAML2 involved interchromosomal translocation, occurred with low fusion burden, was not associated with TP53 mutations, and was previously reported in a pre-cancerous pancreatic disease case, supporting further investigation.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},372745,1791247485,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":8,"category_name":10,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":143,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":67,"update_tm":147,"read_time":148},24464137899374,"https://us-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Article  \nNovel MAML2 Fusions in Human Malignancy †  \nTakefumi Komiya 1, *, Kieran Sweeney 2, Chao H. Huang 3, Anthony Crymes 4, Emmanuel S. Antonarakis 5, Andrew Elliott 2, Matthew J. Oberley 2 and Mark G. Evans 2  \nReceived: 19 August 2025  \nRevised: 24 September 2025  \nAccepted: 24 September 2025  \nPublished: 27 September 2025  \nCitation: Komiya, T.; Sweeney, K.; Huang, C.H.; Crymes, A.; Antonarakis, E.S.; Elliott, A.; Oberley, M.J.; Evans, M.G. Novel MAML2 Fusions in Human Malignancy. Cancers 2025, 17, 3146. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers17193146  \nCopyright: © 2025 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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Division of Hematology and Oncology, Penn State College of Medicine, Hershey, PA 17033, USA  \n2 Caris Life Sciences, Phoenix, AZ 85040, USA; [ksweeney@carisls.com](ksweeney@carisls.com) (K.S.); [aelliott@carisls.com](aelliott@carisls.com) (A.E.); [moberley@carisls.com](moberley@carisls.com) (M.J.O.); [mevans@carisls.com](mevans@carisls.com) (M.G.E.)  \n3 Medical Oncology Division, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66103, USA; [chuang2@kumc.edu](chuang2@kumc.edu)  \n4 Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90007, USA; [acrymes@dhs.lacounty.gov](acrymes@dhs.lacounty.gov)  \n5 Division of Hematology, Oncology and Transplantation, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; [anton401@umn.edu](anton401@umn.edu)  \n* Correspondence: [tkomiya@pennstatehealth.psu.edu](tkomiya@pennstatehealth.psu.edu)  \n† This paper is an extend version of our paper published in Komiya, T.; Sweeney, K.; Huang, C.H.; Crymes, A.; Wang, B.; Antonarakis, E.S.; Elliott, A.; Oberley, M.J.; Evans, M.G. Novel MAML2 fusions as oncogenic drivers in human malignancy. J Clin Oncol, 2025, 43, e15067. [https://doi.org/10.1200/JCO.2025.43.16_suppl.e15067](https://doi.org/10.1200/JCO.2025.43.16_suppl.e15067) .  \nSimple Summary  \nMany gene fusions have been implicated in the development and progression of human cancers. Our group and others have identified specific gene fusions involving the MAML2 gene in human cancers, and we were interested in searching for additional novel MAML2 fusions. Our analysis with the Caris Life Sciences molecular database demonstrated that most of the novel fusions were associated with increased fusion burden and genomic loss of heterozygosity, which are potentially suggestive of genomic instability, except for ATXN3::MAML2 which warrants further investigation.  \nAbstract  \nBackground: Oncogenic fusions of MAML2 with CRTC1, CRTC3, YAP1, and NR1D1 retain the MAML2 transactivating domain (TAD) and are believed to drive aberrant gene transcription. While the oncogenic roles of these known fusions have been established, we aimed to identify novel MAML2 fusions across a range of human malignancies. Methods: DNA and RNA sequencing were performed on tumor samples submitted to Caris Life Sciences. MAML2 fusions were identified from RNA transcripts and filtered to includeonly known pathogenic fusions or recurrent, in-frame fusions containing a C-terminal MAML2 TAD. Fusion burden was defined as the number of unique fusion isoforms per sample. Results: Among 180,124 tumor samples, 143 specimens harbored MAML2 fusions with a MAML2 TAD: >50% of specimens harbored known fusions, but novel fusions with MTMR2 (31/143), SESN3 (11/143), CCDC82 (6/143), FAM76B (4/143), and ATXN3 (3/143) were also identified. Compared to the known fusions, the novel fusions generally had lower expressions (median: 8 vs. 13 junction reads/sample, p = 0.0064), higher fusion burdens (median: 6 vs. 2 un","cbCaimX0iSHVWuvo","https://ap.wps.com/l/cbCaimX0iSHVWuvo","pdf",1839057,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What is MAML2 and why are its fusions important in cancers?\",\"answer\":\"MAML2 is a Mastermind family member that regulates NOTCH signaling by activating downstream transcription. Fusions retaining its transactivating domain can drive aberrant gene transcription and influence malignancy development.\"},{\"question\":\"How were novel MAML2 fusions identified in the study?\",\"answer\":\"Tumor DNA and RNA sequencing from Caris Life Sciences was used to identify MAML2 fusions from RNA transcripts. Fusions were filtered to include only known pathogenic events or recurrent in-frame fusions containing a C-terminal MAML2 TAD.\"},{\"question\":\"What distinguishes the novel MAML2 fusions from the known ones?\",\"answer\":\"Compared with known fusions, novel fusions generally had lower expression, higher fusion burden, more frequent TP53 co-mutations, and no clear association with tissue of origin.\"},{\"question\":\"Why is ATXN3::MAML2 considered potentially pathogenic?\",\"answer\":\"Excluding ATXN3::MAML2, novel partners were typically near MAML2 and likely arose from copy-number changes. In contrast, ATXN3::MAML2 involved interchromosomal translocation, occurred with low fusion burden, was not associated with TP53 mutations, and was previously reported in a pre-cancerous pancreatic disease case, supporting further investigation.\"}]","Novel MAML2 Fusions in Human Malignancy | PDF",1790195272,15]