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Integrative transcriptomic and CRISPR dependency analysis identifies hepatoblastoma-specific essential genes and
Christophe Desterke1, Ana Jarén2, Raquel Francés3
1Université Paris-Saclay, Faculté de Médecine, INSERM-UMRS1310, Villejuif, France.
Cancer Genetics
|July 1, 2026
Summary
This study identifies key genes essential for hepatoblastoma (HB) and develops a predictive signature for tumor identification. It also highlights HDAC11 as a potential therapeutic target for drug repurposing in pediatric cancer.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Hepatoblastoma (HB) is the most common childhood liver cancer, but its molecular drivers are not fully understood.
- Identifying essential genes and biomarkers is crucial for improving diagnosis and treatment.
Purpose of the Study:
- To identify genes essential for hepatoblastoma (HB) growth and survival.
- To develop a molecular signature for accurate tumor identification and patient stratification.
- To uncover potential therapeutic targets and repurposing strategies for HB.
Main Methods:
- Integrated transcriptomic profiling with CRISPR-Cas9 dependency data to identify HB-essential genes.
- Developed a 16-gene predictive signature using Elastic Net regression, validated in independent cohorts.
- Utilized single-cell RNA-seq and deep learning for cell-type-specific expression analysis and tumor classification.
- Analyzed drug-gene interactions to identify actionable therapeutic targets.
Main Results:
- Identified 73 HB-essential genes not found in adult liver cancers.
- The 16-gene signature achieved high accuracy (AUC > 0.99) in distinguishing HB from normal liver.
- Deep learning classifier accurately differentiated tumor cells from hepatocytes, highlighting key gene contributors.
- HDAC11 was identified as a druggable target with potential for repurposing approved pediatric cancer drugs.
Conclusions:
- An integrative approach successfully identified clinically relevant genes and predictive signatures for hepatoblastoma.
- Expression-based scores can aid in patient stratification.
- Targeting HDAC11 with existing pediatric drugs offers a promising strategy for hepatoblastoma treatment.
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