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    Cancer Cell. 2008 Feb;13(2):129-40.

    The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells.

    Joseph NM, Mosher JT, Buchstaller J, Snider P, McKeever PE, Lim M, Conway SJ, Parada LF, Zhu Y, Morrison SJ.

    Center for Stem Cell Biology, Howard Hughes Medical Institute, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA.

    Neurofibromatosis is caused by the loss of neurofibromin (Nf1), leading to peripheral nervous system (PNS) tumors, including neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). A long-standing question has been whether these tumors arise from neural crest stem cells (NCSCs) or differentiated glia. Germline or conditional Nf1 deficiency caused a transient increase in NCSC frequency and self-renewal in most regions of the fetal PNS. However, Nf1-deficient NCSCs did not persist postnatally in regions of the PNS that developed tumors and could not form tumors upon transplantation into adult nerves. Adult P0a-Cre+Nf1(fl/-) mice developed neurofibromas, and Nf1(+/-)Ink4a/Arf(-/-) and Nf1/p53(+/-) mice developed MPNSTs, but NCSCs did not persist postnatally in affected locations in these mice. Tumors appeared to arise from differentiated glia, not NCSCs.

    PMID: 18242513 [PubMed - indexed for MEDLINE]

    PMCID: 2566828

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