title: Sequencing Overview of Ewing Sarcoma: A Journey across Genomic, Epigenomic and Transcriptomic Landscapes.
abstract: Ewing sarcoma is an aggressive neoplasm occurring predominantly in adolescent Caucasians. At the genome level, a pathognomonic EWSR1-ETS translocation is present. The resulting fusion protein acts as a molecular driver in the tumor development and interferes, amongst others, with endogenous transcription and splicing. The Ewing sarcoma cell shows a poorly differentiated, stem-cell like phenotype. Consequently, the cellular origin of Ewing sarcoma is still a hot discussed topic. To further characterize Ewing sarcoma and to further elucidate the role of EWSR1-ETS fusion protein multiple genome, epigenome and transcriptome level studies were performed. In this review, the data from these studies were combined into a comprehensive overview. Presently, classical morphological predictive markers are used in the clinic and the therapy is dominantly based on systemic chemotherapy in combination with surgical interventions. Using sequencing, novel predictive markers and candidates for immuno- and targeted therapy were identified which were summarized in this review.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands. L.G.L.Sand@lumc.nl.
authors.forename: Laurens G L
authors.initials: LG
authors.lastname: Sand
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands. k.szuhai@lumc.nl.
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands. p.c.w.hogendoorn@lumc.nl.
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
mesh_terms: D057890:Epigenomics; D006801:Humans; D058990:Molecular Targeted Therapy; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000628:therapy; D017422:Sequence Analysis, DNA; D059467:Transcriptome / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion
keywords: Ewing sarcoma; bone neoplasm; bone tumor; epigenetics; immunotherapy; micro-environment; next generation sequencing; soft tissue tumor; splicing; targeted therapy