Thickened area of external granular layer and Ki-67 positive focus are early events of medulloblastoma in Ptch1⁺/⁻ mice.

摘要: Abstract Patched1 (Ptch1) encodes a receptor for Sonic hedgehog (Shh) and is major gene related to human medulloblastoma (MB) in the Shh subgroup. MB thought arise from residual granule cell precursors (GCPs) located external granular layer (EGL) of developing cerebellum. As detailed preneoplastic changes remain obscure, we immunohistochemically clarified derived cell, early events MBs, cerebellar developmental processes Ptch1 +/− mice, an animal model In earliest proliferative lesions were detected at PND10 as focal thickened areas outer EGL. This area was composed GCP-like cells with atypia nuclei disarrangement. latter period, foci high incidence outermost Their localization morphological similarities indicated that GCPs There two types foci. A Ki-67-positive focus found mice only. type resembled EGL characterized by having proliferating activity lack neuronal differentiation. Another focus, Ki-67-negative, observed both genotypes exhibited many same features mature internal cells, suggesting had no potential. Due morphological, immunohistochemical characteristics, our results indicate are MB.