一种新型 HMGA2::KITLG融合型脂肪肉瘤伴有MDM2和HMGA2扩增。

IF 3.1 2区 医学 Q2 GENETICS & HEREDITY Genes, Chromosomes & Cancer Pub Date : 2023-09-12 DOI:10.1002/gcc.23200
Shishan Zhou, Changliang Zhang, Zhipeng Zhang, Yongbin Hu, Lina Zhao, Wentao Hu, Si Chen, Bin Li, Sheng Xiao
{"title":"一种新型 HMGA2::KITLG融合型脂肪肉瘤伴有MDM2和HMGA2扩增。","authors":"Shishan Zhou,&nbsp;Changliang Zhang,&nbsp;Zhipeng Zhang,&nbsp;Yongbin Hu,&nbsp;Lina Zhao,&nbsp;Wentao Hu,&nbsp;Si Chen,&nbsp;Bin Li,&nbsp;Sheng Xiao","doi":"10.1002/gcc.23200","DOIUrl":null,"url":null,"abstract":"<p>High-mobility group AT-hook 2 (<i>HMGA2</i>) is rearranged in various types of mesenchymal tumors, particularly lipomas. <i>HMGA2</i> is also co-amplified with mouse double minute 2 (<i>MDM2</i>) in well-differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in-frame fusion between <i>HMGA2</i> and <i>KITLG</i>, which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The <i>HMGA2</i> breakpoint is in intron 3, a commonly observed location for <i>HMGA2</i> rearrangements, while the <i>KITLG</i> breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of <i>KITLG</i>. By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of <i>KITLG</i> caused by its rearrangement with <i>HMGA2</i>, leading to the constitutive activation of KIT kinase. While <i>MDM2</i> amplification was observed in both the primary tumor and the relapsed tumor, the <i>HMGA2::KITLG</i> was only present in the relapsed tumor, indicating the role of <i>HMGA2::KITLG</i> in disease progression.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A novel HMGA2::KITLG fusion in a dedifferentiated liposarcoma with amplification of MDM2 and HMGA2\",\"authors\":\"Shishan Zhou,&nbsp;Changliang Zhang,&nbsp;Zhipeng Zhang,&nbsp;Yongbin Hu,&nbsp;Lina Zhao,&nbsp;Wentao Hu,&nbsp;Si Chen,&nbsp;Bin Li,&nbsp;Sheng Xiao\",\"doi\":\"10.1002/gcc.23200\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>High-mobility group AT-hook 2 (<i>HMGA2</i>) is rearranged in various types of mesenchymal tumors, particularly lipomas. <i>HMGA2</i> is also co-amplified with mouse double minute 2 (<i>MDM2</i>) in well-differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in-frame fusion between <i>HMGA2</i> and <i>KITLG</i>, which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The <i>HMGA2</i> breakpoint is in intron 3, a commonly observed location for <i>HMGA2</i> rearrangements, while the <i>KITLG</i> breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of <i>KITLG</i>. By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of <i>KITLG</i> caused by its rearrangement with <i>HMGA2</i>, leading to the constitutive activation of KIT kinase. While <i>MDM2</i> amplification was observed in both the primary tumor and the relapsed tumor, the <i>HMGA2::KITLG</i> was only present in the relapsed tumor, indicating the role of <i>HMGA2::KITLG</i> in disease progression.</p>\",\"PeriodicalId\":12700,\"journal\":{\"name\":\"Genes, Chromosomes & Cancer\",\"volume\":\"63 1\",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2023-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genes, Chromosomes & Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/gcc.23200\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes, Chromosomes & Cancer","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/gcc.23200","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

高迁移率基团 AT 钩 2(HMGA2)在各种类型的间质肿瘤,尤其是脂肪瘤中发生重排。在分化良好的脂肪肉瘤/分化不良的脂肪肉瘤(WDLPS/DDLPS)中,HMGA2还与小鼠双分化2(MDM2)共同扩增。我们报告了一例复发的DDLPS患者,其HMGA2与KITLG之间存在新型框架内融合,KITLG编码KIT激酶的配体,KIT激酶是一种参与配子发生、造血和黑色素生成的关键蛋白。HMGA2 的断点位于内含子 3,这是 HMGA2 重排的常见位置,而 KITLG 的断点位于内含子 2,导致融合蛋白几乎包含 KITLG 的整个编码序列。通过免疫组化染色,肿瘤细胞表达了 KIT,并显示出磷酸化的 MAPK(KIT 的主要下游靶点)。我们提出了一种致癌机制,即 KITLG 与 HMGA2 重排引起的 KITLG 过表达,从而导致 KIT 激酶的组成性激活。虽然在原发肿瘤和复发肿瘤中都观察到了 MDM2 扩增,但 HMGA2::KITLG 只出现在复发肿瘤中,这表明 HMGA2::KITLG 在疾病进展中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
A novel HMGA2::KITLG fusion in a dedifferentiated liposarcoma with amplification of MDM2 and HMGA2

High-mobility group AT-hook 2 (HMGA2) is rearranged in various types of mesenchymal tumors, particularly lipomas. HMGA2 is also co-amplified with mouse double minute 2 (MDM2) in well-differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in-frame fusion between HMGA2 and KITLG, which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The HMGA2 breakpoint is in intron 3, a commonly observed location for HMGA2 rearrangements, while the KITLG breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of KITLG. By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of KITLG caused by its rearrangement with HMGA2, leading to the constitutive activation of KIT kinase. While MDM2 amplification was observed in both the primary tumor and the relapsed tumor, the HMGA2::KITLG was only present in the relapsed tumor, indicating the role of HMGA2::KITLG in disease progression.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Genes, Chromosomes & Cancer
Genes, Chromosomes & Cancer 医学-遗传学
CiteScore
7.00
自引率
8.10%
发文量
94
审稿时长
4-8 weeks
期刊介绍: Genes, Chromosomes & Cancer will offer rapid publication of original full-length research articles, perspectives, reviews and letters to the editors on genetic analysis as related to the study of neoplasia. The main scope of the journal is to communicate new insights into the etiology and/or pathogenesis of neoplasia, as well as molecular and cellular findings of relevance for the management of cancer patients. While preference will be given to research utilizing analytical and functional approaches, descriptive studies and case reports will also be welcomed when they offer insights regarding basic biological mechanisms or the clinical management of neoplastic disorders.
期刊最新文献
Peter Besmer, PhD Obituary (1940–2024) Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets Fibromyxoid aSoft Tissue Tumor With PLAG1 Fusion—The First Case in an Adult Patient An Inflammatory Myofibroblastic Tumor With a Novel ALKV1180L Mutation Leading to Acquired Resistance to Tyrosine Kinase Inhibitors Novel HMGA2::COL14A1 Fusion Identified in Xanthogranulomatous Epithelial Tumor/Keratin-Positive Giant Cell Tumor
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1