Neurofibromatosis 1 is a hereditary syndrome characterized by the development of numerous benign neurofibromas, a small subset of which progress to malignant peripheral nerve sheath tumors (MPNSTs). To better understand the genetic basis for MPNSTs, we performed genome-wide or targeted sequencing on 50 cases. Sixteen MPNSTs but none of the neurofibromas tested were found to have somatic mutations in SUZ12, implicating it as having a central role in malignant transformation.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Acta Neurochirurgica Open Access 24 November 2021
Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line
Scientific Reports Open Access 11 March 2021
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Carey, J.C. et al. Ann. NY Acad. Sci. 486, 45–56 (1986).
Pasmant, E., Vidaud, M., Vidaud, D. & Wolkenstein, P. J. Med. Genet. 49, 483–489 (2012).
Evans, D.G. et al. J. Med. Genet. 39, 311–314 (2002).
Pasmant, E. et al. Hum. Mutat. 31, E1506–E1518 (2010).
Rahrmann, E.P. et al. Nat. Genet. 45, 756–766 (2013).
Zou, C. et al. Ann. Surg. 249, 1014–1022 (2009).
Liu, C. et al. Tumour Biol. 35, 6073–6082 (2014).
Benoit, Y.D., Laursen, K.B., Witherspoon, M.S., Lipkin, S.M. & Gudas, L.J. J. Cell. Physiol. 228, 764–772 (2013).
Sausen, M. et al. Nat. Genet. 45, 12–17 (2013).
Yuen, B.T. & Knoepfler, P.S. Cancer Cell 24, 567–574 (2013).
Dorschner, M.O., Sybert, V.P., Weaver, M., Pletcher, B.A. & Stephens, K. Hum. Mol. Genet. 9, 35–46 (2000).
López Correa, C., Brems, H., Lazaro, C., Marynen, P. & Legius, E. Am. J. Hum. Genet. 66, 1969–1974 (2000).
Zhang, J. et al. Nature 481, 157–163 (2012).
Brecqueville, M. et al. Blood Cancer J. 1, e33 (2011).
Ntziachristos, P. et al. Nat. Med. 18, 298–301 (2012).
Koontz, J.I. et al. Proc. Natl. Acad. Sci. USA 98, 6348–6353 (2001).
Li, H. et al. Proc. Natl. Acad. Sci. USA 104, 20001–20006 (2007).
Cui, Y., Chen, J., He, Z. & Xiao, Y. Cell. Physiol. Biochem. 31, 778–784 (2013).
Lobry, C., Oh, P., Mansour, M.R., Look, A.T. & Aifantis, I. Blood 123, 2451–2459 (2014).
Bettegowda, C. et al. Oncotarget 4, 572–583 (2013).
We thank our patients for their courage and generosity. We also thank J. Ptak, N. Silliman, L. Dobbyn, J. Schaeffer and M. Papoli for expert technical assistance. The work was supported by the Virginia and D.K. Ludwig Fund for Cancer Research, a Burroughs Wellcome Career Award for Medical Scientists, a Johns Hopkins Clinical Scientist Award and grant 2014107 from the Doris Duke Charitable Foundation.
Under agreements between Johns Hopkins University, Genzyme, Sysmex-Inostics, Qiagen, Invitrogen and Personal Genome Diagnostics, N.P., B.V. and K.W.K. are entitled to a share of the royalties received by Johns Hopkins University on sales of products related to genes and technologies described in this manuscript. N.P., B.V. and K.W.K. are co-founders of Inostics and Personal Genome Diagnostics, are members of their Scientific Advisory Boards and own Personal Genome Diagnostics stock, which is subject to certain restrictions under Johns Hopkins University policy. The terms of these arrangements are managed by Johns Hopkins University in accordance with its conflict-of-interest policies.
Integrated supplementary information
Circos plots representing structural alterations in MPNST tumors that were analyzed via whole-genome sequencing.
Representative H&E, SUZ12 and H3K27me3 immunohistochemistry results from MPNTs with and without SUZ12 alterations. Each image is at 40× magnification and from a representative area of the tumor but not from identical locations given the scarcity of tissue.
About this article
Cite this article
Zhang, M., Wang, Y., Jones, S. et al. Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat Genet 46, 1170–1172 (2014). https://doi.org/10.1038/ng.3116
This article is cited by
EZH2 endorses cell plasticity to non-small cell lung cancer cells facilitating mesenchymal to epithelial transition and tumour colonization
Acta Neurochirurgica (2022)
Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Soft Tissue Tumors
Head and Neck Pathology (2022)
Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor
Laboratory Investigation (2022)