Related Experiment Video
Updated: May 26, 2026

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
Chromatin remodeling-driven stratification and a five-gene RiskScore define proliferative aggressiveness and
Aiguo Zhu1,2, Xin Li1,2, Zhengchao Jin1,2
1Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Chromatin remodeling defines neuroblastoma subtypes and a five-gene risk score predicts patient survival. This score links aggressive tumor biology to specific pathways and potential therapeutic targets.
Area of Science:
- Oncology
- Genetics
- Epigenetics
Background:
- Neuroblastoma exhibits clinical heterogeneity.
- Epigenetic dysregulation, particularly chromatin remodeling, influences aggressive tumor states, prognosis, and therapeutic strategies.
Purpose of the Study:
- Define neuroblastoma subtypes associated with chromatin remodeling.
- Develop a prognostic risk score based on subtype-associated transcriptional changes.
- Validate the score externally and characterize its biological underpinnings.
Main Methods:
- Analyzed a chromatin remodeling gene set in RNA sequencing cohorts.
- Used consensus clustering to define molecular subtypes.
- Employed LASSO Cox regression and multivariable Cox refinement to identify a five-gene signature for the RiskScore.
- Validated the RiskScore using Kaplan-Meier analysis and ROC curves in independent cohorts.
Main Results:
- Chromatin remodeling-based clustering identified prognostically distinct neuroblastoma subtypes.
- The five-gene RiskScore robustly predicted overall survival in development and validation cohorts.
- High-RiskScore tumors showed enhanced cell-cycle and DNA repair programs, indicating an aggressive phenotype.
Conclusions:
- Chromatin remodeling programs reproducibly define neuroblastoma subtypes.
- A stable, externally validated five-gene prognostic RiskScore links aggressive biology to mechanistic pathways.
- The findings support novel therapeutic hypotheses for neuroblastoma.
Related Concept Videos
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Abnormal Proliferation
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
