Canonical TGF-β Pathway Activity Is a Predictor of SHH-Driven Medulloblastoma Survival and Delineates Putative Precursors in Cerebellar Development

摘要: Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Very little known about aggressive forms this disease, such as metastatic or recurrent MBs. In order to identify pathways involved in MB pathophysiology, we performed unbiased, whole genome microarrays on tumors at both human and murine levels. Primary MBs were compared, transcriptomically, their patient-matched tumors. Expression profiling was also from two spontaneously developing mouse models (Ptch+/- Smo/Smo) that present with differing clinical severities. At levels identified transforming growth factor-beta (TGF-β) a potential contributor progression/metastasis. Smad3, major downstream component TGF-β pathway, evaluated using immunohistochemistry tissues shown correlate metastasis survival. Similarly, Smad3 expression during development subset cerebellar neuronal precursors putative cells origin for Smad3-positive To our knowledge, first study links pathogenesis. Our research suggests canonical activation pathway leads better prognosis patients.