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.
Laura A. Pack, PhD, Associate Professor, Scientific secretary of National Research Oncology Center, Astana, the Republic of Kazakhstan; phone: 8 707 101 13 93, e-mail: laura_pak@mail.ru, https://orcid.org/0000-0002-5249-3359
Zhanna B. Mussazhanova - PhD, assistant of professor, Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan and Нigh Medical School, Faculty of Medicine and Health Care, Al Farabi Kazakh National University, Almaty, the Republic of Kazakhstan, phone: 8 180 6479 27 26, e-mail: mussazhanova.zh@gmail.com, https://orcid.org/0000-0002-7315-7725
Aidos K. Bolatov - PhD-student at Shenzhen University Medical School, Shenzhen University (Shenzhen, China), researcher at “University Medical Center” Corporate Fund (Astana, the Republic of Kazakhstan), phone: 8 777 600 00 96, e-mail: bolatovaidos@gmail.com, https://orcid.org/0000-0002-5390-4623
Askhat K. Zhakupov - Medical Doctor, Cytogeneticist, Oncohematologist at “University Medical Center” Corporate Fund, Astana, the Republic of Kazakhstan, phone: 8 705 100 16 59, e-mail: md.zhakupovaskhat@gmail.com, https://orcid.org/0000-0002-0609-9334
Meiram S. Muldakhmetov - Doctor of Medical Sciences, Professor at the Department of Pediatrics with a course in Pulmonology and Nephrology, NJSC “Astana Medical University”, Astana, the Republic of Kazakhstan https://orcid.org/0000-0002-8389-2061
Corresponding author:
Raigul R. Nussupova – PhD student at NJSC “Astana Medical University”, Astana, the Republic of Kazakhstan. Pediatric oncologist-hematologist of the Corporate Fund “University Medical Center” Astana, the Republic of Kazakhstan.
Postal address: The Republic of Kazakhstan, 010000, Astana, Kabanbai Batyr St. 29/1, Block B, Apt. 82.
E-mail: raigul.nussupova@gmail.com
Phone: +7 778 257 59 01
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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.2025.27.1.002Ұқсас жариялымдар:
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