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. 2025 Jun 23;149(1):66.
doi: 10.1007/s00401-025-02907-1.

CNS methylation classifiers may misclassify normal developing cerebellar cortex as medulloblastoma

Jennifer A Cotter  1   2 , Alexander L Markowitz  3 , Everardo Castañeda  3 , Chern-Yu Yen  3 , Dejerianne Ostrow  3 , Debra Hawes  3   4 , Jianling Ji  3   4
Affiliations

CNS methylation classifiers may misclassify normal developing cerebellar cortex as medulloblastoma

Jennifer A Cotter et al. Acta Neuropathol. .
No abstract available

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Appearance of cerebellar external granule cell layer and performance of methylation classification on cerebellar cortex samples before 6 months of age. In late gestation and infancy, the external granular layer (EGL) covers the cerebellar cortex, as seen in CHLA_CB_2 (a). The EGL consists of closely packed primitive-appearing cells with nuclear angulation (b, enlarged from boxed area shown in a) and, at times, irregular contours. Apoptotic bodies and mitotic figures (b, arrow) are common in the EGL. Ki-67 labeling index is elevated in the EGL due to ongoing cell proliferation (c). These features are all developmentally appropriate but can be misinterpreted as subpial spread of an embryonal neoplasm. Using DNA methylation array data, UMAP visualization (d–f) shows immature cerebellar tissue samples (blue crosses) more closely associate with MB_SHH groups (e, enlarged from boxed area shown in (d). Older pediatric samples (blue diamonds) show clustering away from those representing individuals aged < 6 months, and associate with reference controls (f, enlarged from boxed area shown in e)
See this image and copyright information in PMC

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