Authors
Sander Lambo, Susanne N Gröbner, Tobias Rausch, Sebastian M Waszak, Christin Schmidt, Aparna Gorthi, July Carolina Romero, Monika Mauermann, Sebastian Brabetz, Sonja Krausert, Ivo Buchhalter, Jan Koster, Danny A Zwijnenburg, Martin Sill, Jens-Martin Hübner, Norman Mack, Benjamin Schwalm, Marina Ryzhova, Volker Hovestadt, Simon Papillon-Cavanagh, Jennifer A Chan, Pablo Landgraf, Ben Ho, Till Milde, Olaf Witt, Jonas Ecker, Felix Sahm, David Sumerauer, David W Ellison, Brent A Orr, Anna Darabi, Christine Haberler, Dominique Figarella-Branger, Pieter Wesseling, Jens Schittenhelm, Marc Remke, Michael D Taylor, Maria J Gil-da-Costa, Maria Łastowska, Wiesława Grajkowska, Martin Hasselblatt, Peter Hauser, Torsten Pietsch, Emmanuelle Uro-Coste, Franck Bourdeaut, Julien Masliah-Planchon, Valérie Rigau, Sanda Alexandrescu, Stephan Wolf, Xiao-Nan Li, Ulrich Schüller, Matija Snuderl, Matthias A Karajannis, Felice Giangaspero, Nada Jabado, Andreas von Deimling, David TW Jones, Jan O Korbel, Katja von Hoff, Peter Lichter, Annie Huang, Alexander JR Bishop, Stefan M Pfister, Andrey Korshunov, Marcel Kool
Publication date
2019/12/12
Journal
Nature
Volume
576
Issue
7786
Pages
274-280
Publisher
Nature Publishing Group UK
Description
Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis. 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, – 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 …
Scholar articles
S Lambo, SN Gröbner, T Rausch, SM Waszak… - Nature, 2019