The Genomic Landscape of Pediatric Ewing Sarcoma
Menée à partir de 116 échantillons tumoraux prélevés sur 112 patients pédiatriques atteints d'un sarcome d'Ewing, cette étude met notamment en évidence la rareté des mutations somatiques susceptibles de faire l'objet d'une thérapie ciblée
Pediatric Ewing sarcoma is characterized by the expression of chimeric fusions of EWS and ETS family transcription factors, representing a paradigm for studying cancers driven by transcription factor rearrangements. In this study, we describe the somatic landscape of pediatric Ewing sarcoma. These tumors are among the most genetically normal cancers characterized to date with only EWS/ETS rearrangements identified in the majority of tumors. STAG2 loss, however, is present in over 15% of Ewing sarcoma tumors; occurs by point mutation, rearrangement, and likely non-genetic mechanisms; and is associated with disease dissemination. Perhaps the most striking finding is the paucity of mutations in immediately targetable signal transduction pathways, highlighting the need for new therapeutic approaches to target EWS/ETS fusions in this disease.