Er 2018 Revised: 16 January 2019 Accepted: 17 JanuaryReferences 1. Gr ewald, T. G. P. et al. Ewing sarcoma. Nat. Rev. Dis. Prim. four, 5 (2018). two. Ladenstein, R. et al. Primary disseminated Nalfurafine Neuronal Signaling multifocal Ewing sarcoma: benefits with the Demoxepam web Euro-EWING 99 trial. J. Clin. Oncol. 28, 3284?291 (2010). 3. Delattre, O. et al. Gene fusion with an ETS DNA-binding domain brought on by chromosome translocation in human tumours. Nature 359, 162?65 (1992). four. Anderson, N. D. et al. Rearrangement bursts produce canonical gene fusions in bone and soft tissue tumors. Science 361, https://doi.org/10.1126/science. aam8419 (2018). five. Gangwal, K. et al. Microsatellites as EWS/FLI response elements in Ewing’s sarcoma. Proc. Natl Acad. Sci. USA 105, 10149?0154 (2008). 6. Tomazou, E. M. et al. Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1. Cell Rep. 10, 1082?095 (2015). 7. Riggi, N. et al. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to straight activate or repress enhancer elements in Ewing sarcoma. Cancer Cell 26, 668?81 (2014). 8. Tirode, F. et al. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov. 4, 1342?353 (2014). 9. Crompton, B. D. et al. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov. 4, 1326?341 (2014). ten. von Levetzow, C. et al. Modeling initiation of Ewing sarcoma in human neural crest cells. PLoS 1 six, e19305 (2011). 11. Tirode, F. et al. Mesenchymal stem cell features of Ewing tumors. Cancer Cell. 11, 421?29 (2007). 12. Minas, T. Z. et al. Combined experience of six independent laboratories attempting to make an Ewing sarcoma mouse model. Oncotarget 8, 34141?4163 (2017). 13. Lambert, M., Jambon, S., Depauw, S. David-Cordonnier, M-H. Targeting transcription aspects for cancer remedy. Molecules 23, https://doi.org/ 10.3390/molecules23061479 (2018). 14. H pener, J. W. et al. Expression in the second calcitonin/calcitonin generelated peptide gene in Ewing sarcoma cell lines. J. Clin. Endocrinol. Metab. 64, 809?17 (1987). 15. Steenbergh, P. H., H pener, J. W., Zandberg, J., Lips, C. J. Jansz, H. S. A second human calcitonin/CGRP gene. FEBS Lett. 183, 403?07 (1985). 16. Hoovers, J. M. et al. High-resolution chromosomal localization with the human calcitonin/CGRP/IAPP gene members of the family. Genomics 15, 525?29 (1993). 17. Steenbergh, P. H. et al. Structure and expression from the human calcitonin/ CGRP genes. FEBS Lett. 209, 97?03 (1986). 18. Wimalawansa, S. J. Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr. Rev. 17, 533?85 (1996). 19. Wimalawansa, S. J., Morris, H. R. MacIntyre, I. Each alpha- and beta-calcitonin gene-related peptides are present in plasma, cerebrospinal fluid and spinal cord in man. J. Mol. Endocrinol. 3, 247?52 (1989). 20. McLatchie, L. M. et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393, 333?39 (1998). 21. Hay, D. L. What tends to make a CGRP2 receptor? Clin. Exp. Pharmacol. Physiol. 34, 963?71 (2007).Official journal of the Cell Death Differentiation AssociationDallmayer et al. Cell Death and Illness (2019)ten:Page 13 of 1322. van Valen, F., Keck, E. J gens, H. Functional traits of calcitonin gene-related peptide receptors in human Ewing’s sarcoma WE-68 cells. FEBS Lett. 256, 170?74 (1989). 2.