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Publication : Distinct neural stem cell populations give rise to disparate brain tumors in response to N-MYC.

First Author  Swartling FJ Year  2012
Journal  Cancer Cell Volume  21
Issue  5 Pages  601-13
PubMed ID  22624711 Mgi Jnum  J:189301
Mgi Id  MGI:5445028 Doi  10.1016/j.ccr.2012.04.012
Citation  Swartling FJ, et al. (2012) Distinct neural stem cell populations give rise to disparate brain tumors in response to N-MYC. Cancer Cell 21(5):601-13
abstractText  The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally stabilized murine N-myc(T58A) into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem, and forebrain. Transplantation of N-myc(WT) NSCs was insufficient for tumor formation. N-myc(T58A) cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating Sonic Hedgehog (SHH) dependence and SHH independence, respectively. These differences were regulated in part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal.
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