ArticleBrain pathology (Zurich, Switzerland)2026
Molecular profiling of pediatric medulloblastoma in Kazakhstan: Genomic alterations, subgroup distribution, and survival.
Article in Brain pathology (Zurich, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Medulloblastoma is the most common malignant pediatric brain tumor and comprises biologically distinct molecular subgroups with different clinicopathologic and prognostic characteristics. Molecular data from Kazakhstan and other underrepresented regions remain limited, and practical approaches for molecular subgroup assignment using formalin-fixed, paraffin-embedded (FFPE) material are needed in settings where advanced molecular classification is not routinely available. We retrospectively analyzed 40 pediatric medulloblastomas diagnosed between 2015 and 2024 at the Corporate Fund "University Medical Center," Kazakhstan. Archived FFPE tumor material underwent histologic review, immunohistochemical evaluation (β-catenin, YAP1, and GAB1), and whole-exome sequencing. Tumors were assigned to WNT, SHH, or non-WNT/non-SHH categories using a combined morphologic, immunophenotypic, and genomic framework, and clinicopathologic variables and overall survival were evaluated across subgroups. WNT medulloblastomas (n = 7, 17.5%) showed the most canonical profile, characterized by classic histology, uniform β-catenin nuclear positivity, recurrent CTNNB1/APC alterations, and frequent chromosome 6 loss. SHH medulloblastomas (n = 10, 25.0%) were enriched for desmoplastic/nodular morphology, frequent YAP1/GAB1 expression, pathogenic PTCH1/SUFU alterations, and additional events involving TP53, TERT, and focal amplifications in a subset. Non-WNT/non-SHH medulloblastomas (n = 23, 57.5%) showed the greatest genomic heterogeneity, including frequent i17q and broader structural complexity. Clinically, WNT tumors occurred predominantly in older children and had the most favorable survival, whereas non-WNT/non-SHH tumors were the only subgroup associated with metastatic disease at presentation and showed the poorest long-term survival. Overall, pediatric medulloblastoma in this cohort demonstrated subgroup-specific patterns consistent with established biology. The integration of pathology, immunohistochemistry, and sequencing enabled clinically meaningful molecular stratification. These findings expand evidence from an underrepresented setting and support pragmatic, resource-adapted profiling in routine practice.
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