Pediatric surgery international · 2025
Novel CTNNB1 gene mutations reveal critical pathogenic mechanisms in pediatric hepatoblastoma.
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Kumar Sourabh, Sharma Jyoti, Pandey Himani, Jain Vishesh, Dhua Anjan Kumar, Yadav Devendra Kumar, Lal Devi, Goel Prabudh
Аннотация
BACKGROUND: Hepatoblastoma (HB) is the most common primary malignant liver tumor in children, with alterations in the Wnt/β-catenin signaling pathway implicated in up to 90% of cases. The CTNNB1, which codes for β-catenin protein, plays a crucial role in this pathway, but its mutation landscape across diverse populations requires further investigation.
OBJECTIVES: To analyse and characterize the genetic variations in the CTNNB1 across three geographically diverse cohorts of hepatoblastoma patients and understand their potential pathogenic mechanisms.
METHODS: The exome data for 54 hepatoblastoma tissue samples was subjected to quality control and alignment to GRCh38. SNVs were identified using GATK/Mutect2 and annotated using multiple databases. CTNNB1 gene variants were filtered and analyzed using cBioPortal, CONSURF 3.0, STRING database, and VarElect for comprehensive molecular and phenotypic analysis.
RESULTS: CTNNB1 mutations were identified in 88.9% of patients, with 21 unique variants found in 24 patients post-filtering. Exon 3 was most frequently affected, with 17 unique mutations present in 91.66% of mutation-positive patients. The most common variants were c.101G > T (p.Gly34Val), c.98C > T (p.Ser33Phe), and c.98C > A (p.Ser33Tyr). Novel mutations were identified at positions S29 and I35, while additional variations were found in exons 4, 7, 10, and 13.
CONCLUSION: This study identified significant CTNNB1 genetic variations in hepatoblastoma, confirming exon 3 as a critical mutational hotspot. The findings enhance our understanding of HB pathogenesis and suggest potential therapeutic targets, particularly in the Wnt/β-catenin signaling pathway. These mutations may serve as valuable diagnostic and prognostic biomarkers for personalized treatment approaches in pediatric hepatoblastoma.
OBJECTIVES: To analyse and characterize the genetic variations in the CTNNB1 across three geographically diverse cohorts of hepatoblastoma patients and understand their potential pathogenic mechanisms.
METHODS: The exome data for 54 hepatoblastoma tissue samples was subjected to quality control and alignment to GRCh38. SNVs were identified using GATK/Mutect2 and annotated using multiple databases. CTNNB1 gene variants were filtered and analyzed using cBioPortal, CONSURF 3.0, STRING database, and VarElect for comprehensive molecular and phenotypic analysis.
RESULTS: CTNNB1 mutations were identified in 88.9% of patients, with 21 unique variants found in 24 patients post-filtering. Exon 3 was most frequently affected, with 17 unique mutations present in 91.66% of mutation-positive patients. The most common variants were c.101G > T (p.Gly34Val), c.98C > T (p.Ser33Phe), and c.98C > A (p.Ser33Tyr). Novel mutations were identified at positions S29 and I35, while additional variations were found in exons 4, 7, 10, and 13.
CONCLUSION: This study identified significant CTNNB1 genetic variations in hepatoblastoma, confirming exon 3 as a critical mutational hotspot. The findings enhance our understanding of HB pathogenesis and suggest potential therapeutic targets, particularly in the Wnt/β-catenin signaling pathway. These mutations may serve as valuable diagnostic and prognostic biomarkers for personalized treatment approaches in pediatric hepatoblastoma.