# Elucidating the role of the SAGA complex in MYCN-amplified neuroblastoma

> **NIH NIH F32** · DANA-FARBER CANCER INST · 2020 · $71,430

## Abstract

Project Summary/Abstract
Neuroblastoma is the most common tumor of infancy and causes a disproportionate number of children's deaths
due to cancer. Pediatric cancers have relatively few oncogenic mutations relative to adult cancers, and most of
the known genetic drivers of disease involve transcription factors, which cannot be readily drugged. Indeed,
amplification of the transcription factor MYCN occurs in 20-25% of neuroblastomas and is associated with high-
risk disease. The development of new therapies for this disease has been a challenge due to this lack of
“druggable” genetic alterations. However, epigenetic dysregulation is now appreciated to be a major driver of
pediatric cancers and targeting the epigenetic agents that maintain the tumorigenic cell state offers a new
approach to treating these intractable cancers. Genome-scale CRISPR-Cas9 functional genomic screens have
identified that MYCN-amplified neuroblastoma cells are dependent on several members of the histone-modifying
Spt-Ada-Gcn5-acetyltransferase (SAGA) complex. Importantly, this complex has never been studied in the
context of MYCN-amplified neuroblastoma. This proposal will address the hypothesis that this complex is a
critical regulator of the epigenetic state of MYCN-amplified neuroblastoma and is required for cell survival and
tumor maintenance. Aim 1 will discover how genetic and pharmacologic loss of this complex and its histone
acetyltransferase activity impacts MYCN-amplified neuroblastoma survival in vitro and in vivo. Aim 2 will
elucidate the contribution of SAGA complex activity to the epigenetic landscape of neuroblastoma, and the
transcriptional consequences of this activity. This work will expand the understanding of epigenetic factors
controlling MYCN-amplified neuroblastoma, as well as establish this complex as a novel therapeutic target in
this disease of high-clinical need.

## Key facts

- **NIH application ID:** 10048635
- **Project number:** 5F32CA243266-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Clare Felicity Malone
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,430
- **Award type:** 5
- **Project period:** 2019-09-12 → 2022-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048635

## Citation

> US National Institutes of Health, RePORTER application 10048635, Elucidating the role of the SAGA complex in MYCN-amplified neuroblastoma (5F32CA243266-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10048635. Licensed CC0.

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