# Dissecting the Pathogenesis of Ewing Sarcoma with Integrative Genomics

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2020 · $479,795

## Abstract

PROJECT SUMMARY
Ewing sarcoma is a rare tumor that occurs in children and young adults. While Ewing sarcoma is relatively
rare, the biology of this disease is also relevant to non-Ewing sarcomas, and to other cancer subtypes, due to
the presence of the EWS/FLI translocation, the driving event in this disease. Similar translocations involving
ETS transcription factors occur in other malignancies, including prostate cancer. Thus, understanding the
biology of Ewing sarcoma may provide insight into many cancer types. We will investigate the role of
secondary genetic events in the pathogenesis of Ewing sarcoma. These secondary events have been
identified through next-generation sequencing of primary tumors and cell lines. Specifically, we will evaluate
the role of STAG2 in mediating epigenetic and transcriptional changes induced by the driving oncogene in
Ewing sarcoma, EWS/FLI.
In Aim 1, we will use genomic approaches (RNAseq, ChIPseq, WGS, etc.) to assess the mechanistic role of
STAG2 in the regulation of chromatin architecture, transcription, and aneuploidy in Ewing cells. In Aim 2, we
will study the role of STAG2 in progression, maintenance and metastasis in Ewing sarcoma, using functional
studies in Ewing sarcoma cell lines and patient-derived xenografts. In Aim 3, we will determine whether there
is a synthetic lethal dependency on STAG1 when STAG2 is absent in Ewing sarcoma cells. Our central
hypothesis is that STAG2 loss plays a key role in the epigenetic reprogramming that drives the oncogenic
function of EWS/FLI.

## Key facts

- **NIH application ID:** 9849212
- **Project number:** 5R01CA204915-04
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Kimberly Stegmaier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $479,795
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849212

## Citation

> US National Institutes of Health, RePORTER application 9849212, Dissecting the Pathogenesis of Ewing Sarcoma with Integrative Genomics (5R01CA204915-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849212. Licensed CC0.

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