Kumar Sourabh, Sharma Jyoti, Pandey Himani, Jain Vishesh, Dhua Anjan Kumar, Yadav Devendra Kumar, Lal Devi, Goel Prabudh
Department of Paediatric Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Redcliffe Labs, Electronic City, Noida, 201301, India.
Pediatr Surg Int. 2025 Jul 26;41(1):233. doi: 10.1007/s00383-025-06116-5.
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.
To analyse and characterize the genetic variations in the CTNNB1 across three geographically diverse cohorts of hepatoblastoma patients and understand their potential pathogenic mechanisms.
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.
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.
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.
肝母细胞瘤（HB）是儿童最常见的原发性恶性肝肿瘤，高达90%的病例中存在Wnt/β-连环蛋白信号通路改变。编码β-连环蛋白的CTNNB1在该通路中起关键作用，但其在不同人群中的突变情况仍需进一步研究。
分析和表征来自三个地理区域不同的肝母细胞瘤患者队列中CTNNB1的基因变异，并了解其潜在致病机制。
对54份肝母细胞瘤组织样本的外显子组数据进行质量控制并与GRCh38比对。使用GATK/Mutect2识别单核苷酸变异（SNV），并使用多个数据库进行注释。使用cBioPortal、CONSURF 3.0、STRING数据库和VarElect对CTNNB1基因变异进行筛选和分析，以进行全面的分子和表型分析。
88.9%的患者中检测到CTNNB1突变，筛选后在24例患者中发现了21种独特变异。外显子3受影响最频繁，91.66%的突变阳性患者中有17种独特突变。最常见的变异为c.101G＞T（p.Gly34Val）、c.98C＞T（p.Ser33Phe）和c.98C＞A（p.Ser33Tyr）。在S29和I35位置发现了新突变，在外显子4、7、10和13中也发现了其他变异。
本研究在肝母细胞瘤中发现了显著的CTNNB1基因变异，证实外显子3是关键突变热点。这些发现增进了我们对HB发病机制的理解，并提示了潜在治疗靶点，特别是在Wnt/β-连环蛋白信号通路中。这些突变可能作为有价值的诊断和预后生物标志物，用于小儿肝母细胞瘤的个性化治疗方案。
