The Genomic Landscape of Pediatric Ewing Sarcoma

作者：Crompton Brian D; Stewart Chip; Taylor Weiner Amaro; Alexe Gabriela; Kurek Kyle C; Calicchio Monica L; Kiezun Adam; Carter Scott L; Shukla Sachet A; Mehta Swapnil S; Thorner Aaron R; de Torres Carmen; Lavarino Cinzia; Sunol Mariona; McKenna Aaron; Sivachenko Andrey; Cibulskis Kristian; Lawrence Michael S; Stojanov Petar; Rosenberg Mara; Ambrogio Lauren; Auclair Daniel; Seepo Sara; Blumenstiel Brendan; DeFelice Matthew; Imaz Rosshandler Ivan

来源：Cancer Discovery, 2014, 4(11): 1326-1341.

DOI：10.1158/2159-8290.00-13-1037

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 more than 15% of Ewing sarcoma tumors; occurs by point mutation, rearrangement, and likely nongenetic 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.
SIGNIFICANCE: We performed next-generation sequencing of Ewing sarcoma, a pediatric cancer involving bone, characterized by expression of EWS-ETS fusions. We found remarkably few mutations. However, we discovered that loss of STAG2 expression occurs in 15% of tumors and is associated with metastatic disease, suggesting a potential genetic vulnerability in Ewing sarcoma.

• 出版日期2014-11