CNS methylation classifiers may misclassify normal developing cerebellar cortex as medulloblastoma - PubMed (original) (raw)

CNS methylation classifiers may misclassify normal developing cerebellar cortex as medulloblastoma

Jennifer A Cotter et al. Acta Neuropathol. 2025.

No abstract available

PubMed Disclaimer

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)

References

    1. Aldape K, Capper D, von Deimling A, Giannini C, Gilbert MR, Hawkins C et al (2025) cIMPACT-NOW update 9: recommendations on utilization of genome-wide DNA methylation profiling for central nervous system tumor diagnostics. Neuro-Oncol Adv 7:vdae228. 10.1093/noajnl/vdae228 -DOI -PMC -PubMed
    1. Aldinger KA, Thomson Z, Phelps IG, Haldipur P, Deng M, Timms AE et al (2021) Spatial and cell-type transcriptional landscape of human cerebellar development. Nat Neurosci 24:1163–1175. 10.1038/s41593-021-00872-y -DOI -PMC -PubMed
    1. Brändl B, Steiger M, Kubelt C, Rohrandt C, Zhu Z, Evers M et al (2025) Rapid brain tumor classification from sparse epigenomic data. Nat Med 31:840–848. 10.1038/s41591-024-03435-3 -DOI -PMC -PubMed
    1. Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D et al (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469–474. 10.1038/nature26000 -DOI -PMC -PubMed
    1. Leto K, Arancillo M, Becker EBE, Buffo A, Chiang C, Ding B et al (2016) Consensus paper: cerebellar development. Cerebellum Lond Engl 15:789–828. 10.1007/s12311-015-0724-2 -DOI -PMC -PubMed

LinkOut - more resources