Abstract
Sarcomas are a heterogeneous group of malignant tumors that are derived from mesenchymal tissues, including bone, muscle, and cartilage. In the last decade, we have gained significant new insights into the genetic abnormalities that underlie the pathogenesis of these tumors. Specific molecular alterations have been associated with specific histological subtypes of sarcomas, leading to a new classification of many sarcomas. Conventionally grouped in either soft-tissue or bone sarcomas according to the site of their origin, these tumors can now be genetically distinguished in two main groups: those carrying tumor-specific recurrent chromosome aberrations and those with complex karyotypes and variable genetic alterations [1, 2]. Sarcomas with recurrent molecular changes include, among others, Ewing sarcoma, synovial sarcoma, alveolar rhabdomyosarcoma, myxoid liposarcoma and myxoid chondrosarcoma.
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References
Helman LJ, Meltzer P. Mechanisms of sarcoma development. Nat Rev Cancer. 2003;3(9):685–94.
Wunder JS, et al. Opportunities for improving the therapeutic ratio for patients with sarcoma. Lancet Oncol. 2007;8(6):513–24.
Delattre O, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992;359:162–5.
Sorensen PH, et al. A second Ewing’s sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet. 1994;6:146–51.
Jeon IS, et al. A variant Ewing’s sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene. 1995;10:1229–34.
Peter M, et al. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene. 1997;14:1159–64.
Ng TL, et al. Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagn. 2007;9:459–63.
Ginsberg JP, et al. EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing’s sarcoma. J Clin Oncol. 1999;17:1809–14.
Brohl AS, et al. The genomic landscape of the Ewing sarcoma family of tumors reveals recurrent STAG2 mutation. PLoS Genet. 2014;10(7):e1004475.
Crompton BD, et al. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov. 2014;4(11):1326–41.
Tirode F, et al. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov. 2014;4(11):1342–53.
Gangwal K, et al. Microsatellites as EWS/FLI response elements in Ewing’s sarcoma. Proc Natl Acad Sci U S A. 2008;105:10149–54.
Guillon N, et al. The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function. PLoS One. 2009;4:e4932.
Tomazou EM, et al. Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1. Cell Rep. 2015;10:1082–95.
Sheffield NC, et al. DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nat Med. 2017;23:386–95.
Riggi N, et al. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell. 2014;26:668–81.
Rocchi A, et al. CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis. J Clin Invest. 2010;120(3):668–80.
Herrero-MartÃn D, et al. Stable interference of EWS-FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target. Br J Cancer. 2009;101(1):80–90.
Hattinger CM, et al. Prognostic impact of chromosomal aberrations in Ewing tumours. Br J Cancer. 2002;86:1763–9.
Mackintosh C, et al. 1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma. Oncogene. 2012;31:1287–98.
Erkizan HV, et al. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing’s sarcoma. Nat Med. 2009;15:750–6.
Olmos D, et al. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing’s sarcoma: a phase 1 expansion cohort study. Lancet Oncol. 2010;11:129–35.
Pappo AS, et al. R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II sarcoma alliance for research through collaboration study. J Clin Oncol. 2011;29:4541–7.
Theisen ER, Pishas KI, Saund RS, Lessnick SL. Therapeutic opportunities in Ewing sarcoma: EWS-FLI inhibition via LSD1 targeting. Oncotarget. 2016;7:17616–30.
Brenner JC, et al. PARP-1 inhibition as a targeted strategy to treat Ewing’s sarcoma. Cancer Res. 2012;72(7):1608–13.
Gorthi A, et al. EWS–FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma. Nature. 2018;555:387–91.
Ordóñez JL, et al. The PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin. Oncotarget. 2015;6:18875–90.
Engert F, et al. PARP inhibitors sensitize Ewing sarcoma cells to temozolomide-induced apoptosis via the mitochondrial pathway. Mol Cancer Ther. 2015;14:2818–30.
Machado I, et al. Immunohistochemical analysis and prognostic significance of PD-L1, PD-1, and CD8+ tumor-infiltrating lymphocytes in Ewing’s sarcoma family of tumors (ESFT). Virchows Arch. 2018;472:815–24.
Spurny C, et al. Programmed cell death ligand 1 (PD-L1) expression is not a predominant feature in Ewing sarcomas. Pediatr Blood Cancer. 2018;65:e26719.
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Scotlandi, K. (2020). Biology of Ewing Sarcoma. In: Picci, P., et al. Diagnosis of Musculoskeletal Tumors and Tumor-like Conditions. Springer, Cham. https://doi.org/10.1007/978-3-030-29676-6_40
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DOI: https://doi.org/10.1007/978-3-030-29676-6_40
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