GENETIC ANALYSIS OF TP53 AND CTNNB1 MUTATIONS IN PEDIATRIC MEDULLOBLASTOMA: A STUDY FROM KAZAKHSTAN
Background: Medulloblastoma is the most common malignant pediatric brain tumor, exhibiting significant genetic heterogeneity. Mutations in TP53 and CTNNB1 have been implicated in tumorigenesis, prognosis, and treatment response. However, their precise role in medulloblastoma remains incompletely understood. This study aimed to analyze TP53 and CTNNB1 variants in Kazakhstani pediatric medulloblastoma patients and assess their clinical significance.
Methods: A retrospective analysis was conducted on 33 pediatric medulloblastoma cases from 2015 to 2023. Formalin-fixed paraffin-embedded (FFPE) tumor tissues were used for DNA extraction and Sanger sequencing of TP53 (exons 4, 5, 6, 7, 8) and CTNNB1 (exons 3, 4). Genetic variants were classified using ClinVar, ACMG guidelines, and AMP classification. Statistical associations between mutations, clinical features, and outcomes were assessed.
Results: Among 28 successfully sequenced cases, seven TP53 variants were identified: c.214_215delinsTG (p.Pro72Cys), c.215_216delinsGT (p.Pro72Arg), c.300G>A (p.Gln100=), c.356C>G (p.Ala119Gly), c.357C>G (p.Ala119=), c.782+10C>G (splice-region), and c.817C>G (p.Arg273Gly). The p.Pro72Arg variant was significantly associated with metastasis (p = 0.008). The c.356C>G (p.Ala119Gly) variant, previously linked to Li-Fraumeni syndrome, was detected in one case. No variants were found in exons 3 and 4 of CTNNB1.
Conclusion: This study highlights the role of TP53 mutations in medulloblastoma progression, particularly their association with metastasis. The absence of CTNNB1 mutations suggests that WNT pathway activation may be rare in this cohort. Further studies with larger sample sizes and functional validation are needed to clarify the prognostic and therapeutic implications of TP53 mutations in pediatric medulloblastoma.
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Nussupova R.R., Pack L.A., Mussazhanova Zh.B., Bolatov A.K., Zhakupov A.K., Muldakhmetov M.S., Genetic Analysis of TP53 and CTNNB1 Mutations in Pediatric Medulloblastoma: A Study from Kazakhstan // Nauka i Zdravookhranenie [Science & Healthcare]. 2025. Vol.27 (1), pp. 17-25. doi 10.34689/SH.2025.27.1.002Related publications:
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