Format

Send to

Choose Destination
Cancer Discov. 2014 Nov;4(11):1326-41. doi: 10.1158/2159-8290.CD-13-1037. Epub 2014 Sep 3.

The genomic landscape of pediatric Ewing sarcoma.

Author information

1
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, Massachusetts.
2
Eli and Edythe L. Broad Institute, Cambridge, Massachusetts.
3
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, Massachusetts. Eli and Edythe L. Broad Institute, Cambridge, Massachusetts. Bioinformatics Graduate Program, Boston University, Boston, Massachusetts.
4
Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
5
Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
6
Department of Pediatric Oncology, Hospital Sant Joan de Déu, Barcelona, Spain.
7
Eli and Edythe L. Broad Institute, Cambridge, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
8
Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
9
Eli and Edythe L. Broad Institute, Cambridge, Massachusetts. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
10
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, Massachusetts. Eli and Edythe L. Broad Institute, Cambridge, Massachusetts.
11
Eli and Edythe L. Broad Institute, Cambridge, Massachusetts. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts. Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts.
12
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, Massachusetts. Eli and Edythe L. Broad Institute, Cambridge, Massachusetts. kimberly_stegmaier@dfci.harvard.edu.

Abstract

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.

PMID:
25186949
DOI:
10.1158/2159-8290.CD-13-1037
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center