| Autor: |
Kimberly Stegmaier, Jaume Mora, Gad Getz, Todd R. Golub, Mark D. Fleming, Carlos Rodriguez-Galindo, Miguel N. Rivera, Angela Schwarz-Cruz y Celis, Ivan Imaz-Rosshandler, Matthew DeFelice, Brendan Blumenstiel, Sara Seepo, Daniel Auclair, Lauren Ambrogio, Mara Rosenberg, Petar Stojanov, Michael S. Lawrence, Kristian Cibulskis, Andrey Sivachenko, Aaron McKenna, Mariona Suñol, Cinzia Lavarino, Carmen de Torres, Aaron R. Thorner, Swapnil S. Mehta, Sachet A. Shukla, Scott L. Carter, Adam Kiezun, Monica L. Calicchio, Kyle C. Kurek, Gabriela Alexe, Amaro Taylor-Weiner, Chip Stewart, Brian D. Crompton |
| Rok vydání: |
2023 |
| Popis: |
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. Cancer Discov; 4(11); 1326–41. ©2014 AACR.This article is highlighted in the In This Issue feature, p. 1243 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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