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• W4361824677 abstract "<div>Abstract<p>A subset of group 3 medulloblastoma frequently harbors amplification or overexpression of <i>MYC</i> lacking additional focal aberrations, yet it remains unclear whether <i>MYC</i> overexpression alone can induce tumorigenesis and which cells give rise to these tumors. Here, we showed that astrocyte progenitors in the early postnatal cerebellum were susceptible to transformation by <i>MYC</i>. The resulting tumors specifically resembled human group 3 medulloblastoma based on histology and gene-expression profiling. Gene-expression analysis of <i>MYC</i>-driven medulloblastoma cells revealed altered glucose metabolic pathways with marked overexpression of lactate dehydrogenase A (<i>LDHA</i>). <i>LDHA</i> abundance correlated positively with <i>MYC</i> expression and was associated with poor prognosis in human group 3 medulloblastoma. Inhibition of LDHA significantly reduced growth of both mouse and human <i>MYC</i>-driven tumors but had little effect on normal cerebellar cells or SHH-associated medulloblastoma. By generating a new mouse model, we demonstrated for the first time that astrocyte progenitors can be transformed by <i>MYC</i> and serve as the cells of origin for group 3 medulloblastoma. Moreover, we identified <i>LDHA</i> as a novel, specific therapeutic target for this devastating disease.</p>Significance:<p>Insights from a new model identified <i>LDHA</i> as a novel target for group 3 medulloblastoma, paving the way for the development of effective therapies against this disease.</p></div>" @default.
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• W4361824677 date "2023-03-31" @default.
• W4361824677 modified "2023-09-25" @default.
• W4361824677 title "Data from <i>MYC</i> Drives Group 3 Medulloblastoma through Transformation of Sox2⁺ Astrocyte Progenitor Cells" @default.
• W4361824677 doi "https://doi.org/10.1158/0008-5472.c.6511457.v1" @default.
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