Dejin Zheng, Ahmed A Elnegiry, Chenxiang Luo, Mohammed Amine Bendahou, Liangqi Xie, Diana Bell, Yoko Takahashi, Ehab Hanna, George I Mias, Mayra F Tsoi, Bin Gu
{"title":"Brd4::Nutm1 融合基因在体内引发 NUT 癌。","authors":"Dejin Zheng, Ahmed A Elnegiry, Chenxiang Luo, Mohammed Amine Bendahou, Liangqi Xie, Diana Bell, Yoko Takahashi, Ehab Hanna, George I Mias, Mayra F Tsoi, Bin Gu","doi":"10.26508/lsa.202402602","DOIUrl":null,"url":null,"abstract":"<p><p>NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a <i>BRD4::NUTM1</i> fusion gene. Because the <i>BRD4::NUTM1</i> gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the <i>Brd4::Nutm1</i> fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, <i>Brd4::Nutm1</i> can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.</p>","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 7","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11082452/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>Brd4::Nutm1</i> fusion gene initiates NUT carcinoma in vivo.\",\"authors\":\"Dejin Zheng, Ahmed A Elnegiry, Chenxiang Luo, Mohammed Amine Bendahou, Liangqi Xie, Diana Bell, Yoko Takahashi, Ehab Hanna, George I Mias, Mayra F Tsoi, Bin Gu\",\"doi\":\"10.26508/lsa.202402602\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a <i>BRD4::NUTM1</i> fusion gene. Because the <i>BRD4::NUTM1</i> gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the <i>Brd4::Nutm1</i> fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, <i>Brd4::Nutm1</i> can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.</p>\",\"PeriodicalId\":18081,\"journal\":{\"name\":\"Life Science Alliance\",\"volume\":\"7 7\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11082452/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life Science Alliance\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.26508/lsa.202402602\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q1\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life Science Alliance","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.26508/lsa.202402602","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/1 0:00:00","PubModel":"Print","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
Brd4::Nutm1 fusion gene initiates NUT carcinoma in vivo.
NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a BRD4::NUTM1 fusion gene. Because the BRD4::NUTM1 gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the Brd4::Nutm1 fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, Brd4::Nutm1 can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.
期刊介绍:
Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.