# Transcriptomic and epigenetic profiling of neuroblastoma states in response to RBM39 degrader

## TL;DR

This study explores how neuroblastoma cells become resistant to treatment by analyzing changes in their gene activity and epigenetic profiles after degrading a specific protein called RBM39.

## Contribution

The study provides a comprehensive transcriptomic and epigenetic dataset of drug-resistant neuroblastoma cell states following RBM39 degradation.

## Key findings

- Repeated treatment with an RBM39 degrader leads to drug resistance in neuroblastoma models.
- Transcriptomic and epigenetic data reveal changes in resistant adrenergic and mesenchymal cell states.
- The dataset can help identify mechanisms of lineage plasticity and therapeutic resistance in neuroblastoma.

## Abstract

Neuroblastoma accounts for approximately 15% of all pediatric cancer-related deaths, largely due to disease relapse following intensive multimodal therapy. A critical barrier to cure neuroblastoma is the emergence of therapy-resistant tumor cells. Neuroblastoma comprises two major cell states, adrenergic (ADRN) and mesenchymal (MES), which are believed to interconvert and contribute to therapeutic resistance through lineage plasticity. To investigate the mechanisms underlying this plasticity, we subjected human and murine neuroblastoma models to repeated treatment with indisulam, a molecular glue compound that selectively degrades the splicing factor RBM39, until full drug resistance emerged. We then generated datasets from these models, including bulk transcriptomic data, ATAC-seq, and H3K27ac CUT&Tag. These data comprehensively characterize transcriptomic and epigenetic landscapes of resistant ADRN and MES neuroblastoma cell states. We present this resource to facilitate reuse by the scientific community. These datasets may support efforts to decipher lineage switching, identify regulators of therapy resistance, and discover potential therapeutic vulnerabilities in resistant neuroblastoma.