• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >The molecular landscape of ETMR at diagnosis and relapse
【24h】

The molecular landscape of ETMR at diagnosis and relapse

机译：ETMR在诊断和复发时的分子格局

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis(1). Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC(2-4) was not amplified frequently had germline mutations in DICER1 or other microRNA-related aberrations such as somatic amplification of miR-17-92 (also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.
机译：具有多层玫瑰花结（ETMR）的胚胎肿瘤是侵袭性的小儿胚胎脑肿瘤，预后普遍较差（1）。在这里，我们收集了193个原发性ETMR和23个匹配的复发样本，以研究这种独特肿瘤类型的基因组格局。我们发现肿瘤患者中建议的驱动程序C19MC（2-4）未被频繁扩增，其DICER1或其他与microRNA相关的畸变（例如miR-17-92的体细胞扩增，也称为MIR17HG）具有种系突变。全基因组测序显示，肿瘤的单核苷酸变异（SNV）总体复发率较低，但由于广泛存在的R环结构而导致普遍的基因组不稳定。我们表明，R环相关的染色体不稳定性可以由DICER1功能的丧失引起。比较原发肿瘤和匹配的复发样本显示出结构变异的保守性很强，但SNV的保守性却很低。此外，许多新获得的SNV与与顺铂治疗有关的突变特征相关。最后，我们证明了使用拓扑异构酶和PARP抑制剂靶向R环可能是这种致命疾病的有效治疗策略。

著录项

  • 来源
    《Nature》 |2019年第7786期|274-280|共7页
  • 作者

    Lambo Sander; Groebner Susanne N.; Rausch Tobias; Waszak Sebastian M.; Schmidt Christin; Gorthi Aparna; Romero July Carolina; Mauermann Monika; Brabetz Sebastian; Krausert Sonja; Buchhalter Ivo; Koster Jan; Zwijnenburg Danny A.; Sill Martin; Huebner Jens-Martin; Mack Norman; Schwalm Benjamin; Ryzhova Marina; Hovestadt Volker; Papillon-Cavanagh Simon; Chan Jennifer A.; Landgraf Pablo; Ho Ben; Milde Till; Witt Olaf; Ecker Jonas; Sahm Felix; Sumerauer David; Ellison David W.; Orr Brent A.; Darabi Anna; Haberler Christine; Figarella-Branger Dominique; Wesseling Pieter; Schittenhelm Jens; Remke Marc; Taylor Michael D.; Gil-da-Costa Maria J.; Lastowska Maria; Grajkowska Wieslawa; Hasselblatt Martin; Hauser Peter; Pietsch Torsten; Uro-Coste Emmanuelle; Bourdeaut Franck; Masliah-Planchon Julien; Rigau Valerie; Alexandrescu Sanda; Wolf Stephan; Li Xiao-Nan; Schuller Ulrich; Snuderl Matija; Karajannis Matthias A.; Giangaspero Felice; Jabado Nada; von Deimling Andreas; Jones David T. W.; Korbel Jan O.; von Hoff Katja; Lichter Peter; Huang Annie; Bishop Alexander J. R.; Pfister Stefan M.; Korshunov Andrey; Kool Marcel;

  • 作者单位

    Hopp Childrens Canc Ctr KiTZ Heidelberg Germany|German Canc Res Ctr Div Pediat Neurooncol Heidelberg Germany|German Canc Res Ctr German Canc Consortium DKTK Heidelberg Germany;

    European Mol Biol Lab Genome Biol Unit Heidelberg Germany;

    Univ Texas Hlth San Antonio Dept Cell Syst & Anat San Antonio TX USA|Univ Texas Hlth San Antonio Greehey Childrens Canc Res Inst San Antonio TX USA;

    German Canc Res Ctr Omics IT & Data Management Core Facil Heidelberg Germany;

    Acad Med Ctr Dept Oncogenom Amsterdam Netherlands;

    NN Burdenko Inst Neurosurg Dept Neuropathol Moscow Russia;

    German Canc Res Ctr Div Mol Genet Heidelberg Germany;

    McGill Univ Ctr Hlth Dept Pediat Montreal PQ Canada;

    Univ Calgary Dept Pathol & Lab Med Calgary AB Canada;

    Univ Cologne Fac Med Dept Pediat Pediat Oncol & Hematol Cologne Germany|Univ Cologne Univ Hosp Cologne Cologne Germany;

    Hosp Sick Children Arthur & Sonia Labatt Brain Tumour Res Ctr Div Hematol Oncol Toronto ON Canada;

    Univ Cologne Fac Med Dept Pediat Pediat Oncol & Hematol Cologne Germany|Univ Cologne Univ Hosp Cologne Cologne Germany|German Canc Res Ctr Clin Cooperat Unit Pediat Oncol Heidelberg Germany|Heidelberg Univ Hosp Dept Pediat Oncol Hematol & Immunol Heidelberg Germany;

    Hopp Childrens Canc Ctr KiTZ Heidelberg Germany|German Canc Res Ctr Clin Cooperat Unit Pediat Oncol Heidelberg Germany|Heidelberg Univ Hosp Dept Pediat Oncol Hematol & Immunol Heidelberg Germany;

    Hopp Childrens Canc Ctr KiTZ Heidelberg Germany|German Canc Res Ctr German Canc Consortium DKTK Heidelberg Germany|Heidelberg Univ Hosp Dept Neuropathol Heidelberg Germany|German Canc Res Ctr Clin Cooperat Unit Neuropathol Heidelberg Germany;

    Univ Hosp Motol Dept Pediat Hematol & Oncol Prague Czech Republic;

    St Jude Childrens Res Hosp Dept Pathol 332 N Lauderdale St Memphis TN 38105 USA;

    Lund Univ Fac Med Dept Clin Sci Lund Neurosurg Sect Lund Sweden;

    Med Univ Vienna Inst Neurol Vienna Austria;

    Aix Marseille Univ Neurophysiopathol Inst INP CNRS Marseille France|APHM Dept Pathol Marseille France;

    Princess Maxima Ctr Pediat Oncol Utrecht Netherlands|Univ Amsterdam Med Ctr Locat VUmc Dept Pathol Amsterdam Netherlands;

    Univ Hosp Tubingen Inst Pathol & Neuropathol Dept Neuropathol Tubingen Germany|Univ Hosp Tubingen Comprehens Canc Ctr Tubingen Stuttgart Ctr CNS Tumors Tubingen Germany;

    German Canc Res Ctr German Canc Consortium DKTK Heidelberg Germany|Univ Hosp Dusseldorf Fac Med Dept Pediat Oncol Hematol & Clin Immunol Dusseldorf Germany|Univ Toronto Hosp Sick Children Arthur & Sonia Labatt Brain Tumor Res Ctr Div Neurosurg Toronto ON Canada;

    Univ Toronto Hosp Sick Children Arthur & Sonia Labatt Brain Tumor Res Ctr Div Neurosurg Toronto ON Canada;

    Univ Hosp Sao Joao Alameda Hernani Monteiro Pediat Hematol & Oncol Div Porto Portugal;

    Childrens Mem Hlth Inst Dept Pathol Warsaw Poland;

    Univ Hosp Munster Inst Neuropathol Munster Germany;

    Semmelweis Univ Dept Pediat 2 Budapest Hungary;

    Univ Bonn German Soc Neuropathol & Neuroanat Brain Tumor Reference Ctr Inst Neuropathol Med Ctr Bonn Germany;

    Toulouse Univ Hosp Dept Pathol Toulouse France|CRCT INSERM U1037 Toulouse France;

    Paris Sci Lettres Res Univ Lab Translat Res Pediat Oncol SIREDO Pediat Oncol Ctr Inst Curie INSERM U830 Paris France;

    Curie Inst SIREDO Pediat Oncol Ctr Dept Pediat Oncol Paris France|Paris Sci & Lettres Res Univ Inst Curie Hosp Lab Somat Genet Paris France;

    Montpellier Univ Med Ctr Dept Pathol Montpellier France|Montpellier Univ Hosp INM INSERM U1051 Montpellier France;

    Harvard Med Sch Boston Childrens Hosp Dept Pathol Boston MA 02115 USA;

    German Canc Res Ctr High Throughput Sequencing Unit Genom & Prote Core Facil Heidelberg Germany;

    Baylor Coll Med Dept Pediat Texas Childrens Canc Ctr Brain Tumor Program Houston TX 77030 USA|Ann & Robert H Lurie Childrens Hosp Chicago Chicago IL USA|Northwestern Univ Feinberg Sch Med Chicago IL 60611 USA;

    Univ Med Ctr Inst Neuropathol Hamburg Germany|Childrens Canc Ctr Res Inst Hamburg Germany|Univ Med Ctr Dept Pediat Hematol & Oncol Hamburg Germany;

    NYU Langone Hlth Dept Pathol New York NY USA;

    Stephen D Hassenfeld Childrens Ctr Canc & Blood D NYU Langone Med Ctr Div Pediat Hematol Oncol New York NY USA;

    Sapienza Univ Rome Dept Radiol Oncol & Anatomopathol Sci Rome Italy|IRCCS Neuromed Mediterranean Neurol Inst Pozzilli Italy;

    Hopp Childrens Canc Ctr KiTZ Heidelberg Germany|Heidelberg Univ Hosp Dept Neuropathol Heidelberg Germany|German Canc Res Ctr Clin Cooperat Unit Neuropathol Heidelberg Germany;

    Hopp Childrens Canc Ctr KiTZ Heidelberg Germany|German Canc Res Ctr German Canc Consortium DKTK Heidelberg Germany|German Canc Res Ctr Pediat Glioma Res Grp Heidelberg Germany;

    Charite Dept Pediat Oncol Hematol Berlin Germany|Univ Hosp Hamburg Eppendorf Dept Pediat Hematol & Oncol Hamburg Germany;

    German Canc Res Ctr German Canc Consortium DKTK Heidelberg Germany|German Canc Res Ctr Div Mol Genet Heidelberg Germany;

    Hosp Sick Children Arthur & Sonia Labatt Brain Tumour Res Ctr Div Hematol Oncol Toronto ON Canada|Univ Toronto Dept Pediat Med Biophys Lab Med & Pathobiol Toronto ON Canada;

    Univ Texas Hlth San Antonio Dept Cell Syst & Anat San Antonio TX USA|Univ Texas Hlth San Antonio Greehey Childrens Canc Res Inst San Antonio TX USA|Univ Texas Hlth San Antonio Mays Canc Ctr San Antonio TX USA;

    Hopp Childrens Canc Ctr KiTZ Heidelberg Germany|German Canc Res Ctr Div Pediat Neurooncol Heidelberg Germany|German Canc Res Ctr German Canc Consortium DKTK Heidelberg Germany|Heidelberg Univ Hosp Dept Pediat Oncol Hematol & Immunol Heidelberg Germany;

    Heidelberg Univ Hosp Dept Neuropathol Heidelberg Germany|German Canc Res Ctr Clin Cooperat Unit Neuropathol Heidelberg Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号