% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Lambo:148322, author = {S. Lambo$^*$ and S. Gröbner$^*$ and T. Rausch and S. M. Waszak and C. Schmidt and A. Gorthi and J. C. Romero and M. Mauermann$^*$ and S. Brabetz$^*$ and S. Krausert$^*$ and I. Buchhalter$^*$ and J. Koster and D. A. Zwijnenburg and M. Sill$^*$ and J.-M. Hübner$^*$ and N. Mack$^*$ and B. Schwalm$^*$ and M. Ryzhova and V. Hovestadt$^*$ and S. Papillon-Cavanagh and J. A. Chan and P. Landgraf and B. Ho and T. Milde$^*$ and O. Witt$^*$ and J. Ecker$^*$ and F. Sahm$^*$ and D. Sumerauer and D. W. Ellison and B. A. Orr and A. Darabi and C. Haberler and D. Figarella-Branger and P. Wesseling and J. Schittenhelm and M. Remke$^*$ and M. D. Taylor and M. J. Gil-da-Costa and M. Łastowska and W. Grajkowska and M. Hasselblatt and P. Hauser and T. Pietsch and E. Uro-Coste and F. Bourdeaut and J. Masliah-Planchon and V. Rigau and S. Alexandrescu and S. Wolf$^*$ and X.-N. Li and U. Schüller and M. Snuderl and M. A. Karajannis and F. Giangaspero and N. Jabado and A. von Deimling$^*$ and D. T. W. Jones$^*$ and J. O. Korbel and K. von Hoff and P. Lichter$^*$ and A. Huang and A. J. R. Bishop and S. M. Pfister$^*$ and A. Korshunov$^*$ and M. Kool$^*$}, title = {{T}he molecular landscape of {ETMR} at diagnosis and relapse.}, journal = {Nature}, volume = {576}, number = {7786}, issn = {1476-4687}, address = {London [u.a.]}, publisher = {Nature Publ. Group52462}, reportid = {DKFZ-2019-02880}, pages = {274-280}, year = {2019}, note = {#EA:B062#LA:B062#2019 Dec;576(7786):274-280}, abstract = {Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. 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 C19MC2-4 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.}, cin = {B062 / L101 / W610 / B060 / B310 / B300 / W190 / B360}, ddc = {500}, cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)L101-20160331 / I:(DE-He78)W610-20160331 / I:(DE-He78)B060-20160331 / I:(DE-He78)B310-20160331 / I:(DE-He78)B300-20160331 / I:(DE-He78)W190-20160331 / I:(DE-He78)B360-20160331}, pnm = {312 - Functional and structural genomics (POF3-312)}, pid = {G:(DE-HGF)POF3-312}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:31802000}, doi = {10.1038/s41586-019-1815-x}, url = {https://inrepo02.dkfz.de/record/148322}, }