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Neurofibromas in NF1: Schwann Cell Origin and Role of Tumor Environment
Open accessAbstract
Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose functional loss results in the development of benign neurofibromas that can progress to malignancy. Neurofibromas are complex tumors composed of axonal processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through use of a conditional ( cre / lox ) allele, we show that loss of NF1 in the Schwann cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic as well as heterozygosity in non-neoplastic cells. The requirement for a permissive haploinsufficient environment to allow tumorigenesis may have therapeutic implications for NF1 and other familial cancers.
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Cites
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Coussens, L. M., Tinkle, C. L., Hanahan, D., & Werb, Z. (2000) · Cell · doi:10.1016/s0092-8674(00)00139-2 · Cited by 1,306
Cited by
Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.020 · Cited by 7,575
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Mueller, M. M., & Fusenig, N. E. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1477 · Cited by 1,765
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Schubbert, S., Shannon, K., & Bollag, G. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2109 · Cited by 1,583
Normal Stem Cells and Cancer Stem Cells: The Niche Matters
Li, L., & Neaves, W. B. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3986 · Cited by 675
The NF1 tumor suppressor critically regulates TSC2 and mTOR
Johannessen, C. M., Reczek, E. E., James, M. F., Brems, H., Legius, E., & Cichowski, K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503224102 · Cited by 601
Metadata
- Authors
- Zhu, Y., Ghosh, P., Charnay, P., Burns, D. K., & Parada, L. F.
- Venue
- Science
- Published
- 2002-05-03
- Volume
- 296
- Issue
- 5569
- Pages
- 920-922
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2054674800
- Cited by
- 633
- References
- 1
- FWCI
- 19.67
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhu, Y., Ghosh, P., Charnay, P., Burns, D. K., & Parada, L. F. (2002). Neurofibromas in NF1: Schwann Cell Origin and Role of Tumor Environment. Science. https://doi.org/10.1126/science.1068452
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