{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:07:09Z","timestamp":1789927629484,"version":"4.0.1"},"reference-count":228,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FOC"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:p>\n                    Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disease characterized by complex and multicellular neurofibroma tumors, and less frequently by malignant peripheral nerve sheath tumors (MPNSTs) and optic nerve gliomas. Significant advances have been made in elucidating the cellular, genetic, and molecular biology involved in tumor formation in NF1. Neurofibromatosis Type 1 is caused by germline mutations of the\n                    <jats:italic>NF1<\/jats:italic>\n                    tumor suppressor gene, which generally result in decreased intracellular neurofibromin protein levels, leading to increased cascade Ras signaling to its downstream effectors. Multiple key pathways are involved with the development of tumors in NF1, including Ras\/mitogen-activated protein kinase (MAPK) and Akt\/mammalian target of rapamycin (mTOR). Interestingly, recent studies demonstrate that multiple other developmental syndromes (in addition to NF1) share phenotypic features resulting from germline mutations in genes responsible for components of the Ras\/MAPK pathway. In general, a somatic loss of the second\n                    <jats:italic>NF1<\/jats:italic>\n                    allele, also referred to as loss of heterozygosity, in the progenitor cell, either the Schwann cell or its precursor, combined with haploinsufficiency in multiple supporting cells is required for tumor formation. Importantly, a complex series of interactions with these other cell types in neurofibroma tumorigenesis is mediated by abnormal expression of growth factors and their receptors and modification of gene expression, a key example of which is the process of recruitment and involvement of the\n                    <jats:italic>NF1<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    heterozygous mast cell. In general, for malignant transformation to occur, there must be accumulation of additional mutations of multiple genes including\n                    <jats:italic>INK4A\/ARF<\/jats:italic>\n                    and\n                    <jats:italic>P53,<\/jats:italic>\n                    with resulting abnormalities of their respective signal cascades. Further, abnormalities of the\n                    <jats:italic>NF1<\/jats:italic>\n                    gene and molecular cascade described above have been implicated in the tumorigenesis of NF1 and some sporadically occurring gliomas, and thus, these treatment options may have wider applicability. Finally, increased knowledge of molecular and cellular mechanisms involved with NF1 tumorigenesis has led to multiple preclinical and clinical studies of targeted therapy, including the mTOR inhibitor rapamycin, which is demonstrating promising preclinical results for treatment of MPNSTs and gliomas.\n                  <\/jats:p>","DOI":"10.3171\/2009.11.focus09221","type":"journal-article","created":{"date-parts":[[2009,12,31]],"date-time":"2009-12-31T11:26:33Z","timestamp":1262258793000},"page":"E8","source":"Crossref","is-referenced-by-count":115,"title":["Neurofibromatosis Type 1 and tumorigenesis: molecular mechanisms and therapeutic implications"],"prefix":"10.3171","volume":"28","author":[{"given":"Oren N.","family":"Gottfried","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Viskochil","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetics, University of Utah, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Couldwell","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-0280008","series-title":"J Biol Chem","first-page":"16409","article-title":"Structural differences in the minimal catalytic domains of the GTPase-activating proteins p120GAP and neurofibromin","volume":"271","author":"Ahmadian","year":"1996"},{"key":"b2-0280008","series-title":"Expert Rev Neurother","first-page":"535","article-title":"Gliomas in patients with neurofibromatosis type 1","volume":"9","author":"Albers","year":"2009"},{"key":"b3-0280008","series-title":"J Neurol Sci","first-page":"69","article-title":"Neurofibromatosis xenografts. Contribution to pathogenesis","volume":"74","author":"Appenzeller","year":"1986"},{"key":"b4-0280008","series-title":"Hum Mol Genet","first-page":"237","article-title":"Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1","volume":"9","author":"Ars","year":"2000"},{"key":"b5-0280008","series-title":"Cancer Res","first-page":"8573","article-title":"Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity","volume":"63","author":"Bajenaru","year":"2003"},{"key":"b6-0280008","series-title":"Cell","first-page":"851","article-title":"The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins","volume":"63","author":"Ballester","year":"1990"},{"key":"b7-0280008","series-title":"Nature","first-page":"713","article-title":"Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients","volume":"356","author":"Basu","year":"1992"},{"key":"b8-0280008","series-title":"Biochim Biophys Acta","first-page":"43","article-title":"Neurofibromatosis type 1 and Ras-mediated signaling: filling in the GAPs","volume":"1242","author":"Bernards","year":"1995"},{"key":"b9-0280008","series-title":"DNA Cell Biol","first-page":"727","article-title":"Complete human NF1 cDNA sequence: two alternatively spliced mRNAs and absence of expression in a neuroblastoma line","volume":"11","author":"Bernards","year":"1992"},{"key":"b10-0280008","series-title":"Int J Cancer","article-title":"Preclinical in vivo evaluation of rapamycin in human malignant peripheral nerve sheath explant xenograft","author":"Bhola","year":"2009"},{"key":"b11-0280008","series-title":"Lab Invest","first-page":"833","article-title":"Rb and TP53 pathway alterations in sporadic and NF1-related malignant peripheral nerve sheath tumors","volume":"81","author":"Birindelli","year":"2001"},{"key":"b12-0280008","series-title":"Mol Cell Biol","first-page":"3964","article-title":"Ral overactivation in malignant peripheral nerve sheath tumors","volume":"29","author":"Bodempudi","year":"2009"},{"key":"b13-0280008","series-title":"Nat Genet","first-page":"144","article-title":"Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells","volume":"12","author":"Bollag","year":"1996"},{"key":"b14-0280008","series-title":"Nature","first-page":"576","article-title":"Differential regulation of rasGAP and neurofibromatosis gene product activities","volume":"351","author":"Bollag","year":"1991"},{"key":"b15-0280008","series-title":"Genes Dev","first-page":"1019","article-title":"Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues","volume":"8","author":"Brannan","year":"1994"},{"key":"b16-0280008","series-title":"Lancet Oncol","first-page":"508","article-title":"Mechanisms in the pathogenesis of malignant tumours in neurofibromatosis type 1","volume":"10","author":"Brems","year":"2009"},{"key":"b17-0280008","series-title":"Nature","first-page":"291","article-title":"Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway","volume":"347","author":"Buchberg","year":"1990"},{"key":"b18-0280008","series-title":"Surgical Pathology of the Nervous System and Its Coverings","author":"Burger","year":"2002"},{"key":"b19-0280008","series-title":"Cell","first-page":"193","article-title":"A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations","volume":"62","author":"Cawthon","year":"1990"},{"key":"b20-0280008","series-title":"Science","first-page":"2172","article-title":"Mouse models of tumor development in neurofibromatosis type 1","volume":"286","author":"Cichowski","year":"1999"},{"key":"b21-0280008","series-title":"Science","first-page":"1332","article-title":"Reovirus therapy of tumors with activated Ras pathway","volume":"282","author":"Coffey","year":"1998"},{"key":"b22-0280008","series-title":"Nature","first-page":"860","article-title":"Inflammation and cancer","volume":"420","author":"Coussens","year":"2002"},{"key":"b23-0280008","series-title":"J Exp Med","first-page":"F23","article-title":"Inflammatory cells and cancer: think different!","volume":"193","author":"Coussens","year":"2001"},{"key":"b24-0280008","series-title":"Neuron","first-page":"415","article-title":"The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes","volume":"8","author":"Daston","year":"1992"},{"key":"b25-0280008","series-title":"Cell","first-page":"265","article-title":"Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis","volume":"69","author":"DeClue","year":"1992"},{"key":"b26-0280008","series-title":"J Med Genet","first-page":"695","article-title":"Clinical and molecular aspects of RAS related disorders","volume":"45","author":"Denayer","year":"2008"},{"key":"b27-0280008","series-title":"Curr Opin Genet Dev","first-page":"49","article-title":"Ras signalling and apoptosis","volume":"8","author":"Downward","year":"1998"},{"key":"b28-0280008","series-title":"Proc Natl Acad Sci U S A","first-page":"7686","article-title":"A synthetic inhibitor of the mitogen-activated protein kinase cascade","volume":"92","author":"Dudley","year":"1995"},{"key":"b29-0280008","series-title":"Dev Biol","first-page":"235","article-title":"Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4","volume":"188","author":"Dunn","year":"1997"},{"key":"b30-0280008","series-title":"J Intellect Disabil Res","first-page":"838","article-title":"From mTOR to cognition: molecular and cellular mechanisms of cognitive impairments in tuberous sclerosis","volume":"53","author":"Ehninger","year":"2009"},{"key":"b31-0280008","series-title":"Am J Hum Genet","first-page":"393","article-title":"Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1","volume":"66","author":"Eisenbarth","year":"2000"},{"key":"b32-0280008","series-title":"Am J Med Genet","first-page":"325","article-title":"Neurofibromatosis type I (NFI) in Israeli families: linkage analysis as a diagnostic tool","volume":"53","author":"Elyakim","year":"1994"},{"key":"b33-0280008","series-title":"Am J Hum Genet","first-page":"790","article-title":"Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain","volume":"66","author":"Fahsold","year":"2000"},{"key":"b34-0280008","series-title":"J Biol Chem","first-page":"18623","article-title":"Identification of a novel inhibitor of mitogen-activated protein kinase kinase","volume":"273","author":"Favata","year":"1998"},{"key":"b35-0280008","series-title":"Neurofibromatosis: Phenotype, Natural History, and Pathogenesis","first-page":"110","article-title":"Clinical genetics","author":"Friedman","year":"1999"},{"key":"b36-0280008","series-title":"Eur J Neurosci","first-page":"77","article-title":"Fibroblast growth factors and insulin growth factors combine to promote survival of rat Schwann cell precursors without induction of DNA synthesis","volume":"7","author":"Gavrilovic","year":"1995"},{"key":"b37-0280008","series-title":"Genes Chromosomes Cancer","first-page":"62","article-title":"Molecular and cytogenetic analysis of tumors in von Recklinghausen neurofibromatosis","volume":"3","author":"Glover","year":"1991"},{"key":"b38-0280008","series-title":"Neurosurgery","first-page":"1","article-title":"Molecular, genetic, and cellular pathogenesis of neurofibromas and surgical implications","volume":"58","author":"Gottfried","year":"2006"},{"key":"b39-0280008","series-title":"Oncogene","first-page":"507","article-title":"Ras-GTP levels are elevated in human NF1 peripheral nerve tumors","volume":"12","author":"Guha","year":"1996"},{"key":"b40-0280008","series-title":"Cell Growth Differ","first-page":"315","article-title":"Expression of the neurofibromatosis 1 (NF1) isoforms in developing and adult rat tissues","volume":"6","author":"Gutmann","year":"1995"},{"key":"b41-0280008","series-title":"Cell","first-page":"57","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000"},{"key":"b42-0280008","series-title":"Cancer Res","first-page":"1520","article-title":"Preclinical cancer therapy in a mouse model of neurofibromatosis-1 optic glioma","volume":"68","author":"Hegedus","year":"2008"},{"key":"b43-0280008","series-title":"Neurosurgery","first-page":"685","article-title":"Using mice to decipher the molecular genetics of brain tumors","volume":"53","author":"Hesselager","year":"2003"},{"key":"b44-0280008","series-title":"Cancer Res","first-page":"6107","article-title":"Signaling events downstream of mammalian target of rapamycin complex 2 are attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor suppressors","volume":"69","author":"Huang","year":"2009"},{"key":"b45-0280008","series-title":"J Exp Med","first-page":"181","article-title":"Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo","volume":"191","author":"Ingram","year":"2000"},{"key":"b46-0280008","series-title":"Nat Genet","first-page":"353","article-title":"Tumour predisposition in mice heterozygous for a targeted mutation in Nf1","volume":"7","author":"Jacks","year":"1994"},{"key":"b47-0280008","series-title":"Nature","first-page":"558","article-title":"Paternal origin of new mutations in von Recklinghausen neurofibromatosis","volume":"343","author":"Jadayel","year":"1990"},{"key":"b48-0280008","series-title":"Microsc Res Tech","first-page":"393","article-title":"Origin and early development of Schwann cells","volume":"41","author":"Jessen","year":"1998"},{"key":"b49-0280008","series-title":"Cancer Genet Cytogenet","first-page":"138","article-title":"Cytogenetic analysis of soft tissue sarcomas. Recurrent chromosome abnormalities in malignant peripheral nerve sheath tumors (MPNST)","volume":"78","author":"Jhanwar","year":"1994"},{"key":"b50-0280008","series-title":"Curr Biol","first-page":"56","article-title":"TORC1 is essential for NF1-associated malignancies","volume":"18","author":"Johannessen","year":"2008"},{"key":"b51-0280008","series-title":"Proc Natl Acad Sci U S A","first-page":"8573","article-title":"The NF1 tumor suppressor critically regulates TSC2 and mTOR","volume":"102","author":"Johannessen","year":"2005"},{"key":"b52-0280008","series-title":"J Med Genet","first-page":"44","article-title":"A search for evidence of somatic mutations in the NF1 gene","volume":"37","author":"John","year":"2000"},{"key":"b53-0280008","series-title":"Cancer Cell","first-page":"129","article-title":"The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells","volume":"13","author":"Joseph","year":"2008"},{"key":"b54-0280008","series-title":"Expert Rev Mol Med","first-page":"e30","article-title":"Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways","volume":"11","author":"Katz","year":"2009"},{"key":"b55-0280008","series-title":"Oncogene","first-page":"325","article-title":"Schwann cells from neurofibromin deficient mice exhibit activation of p21ras, inhibition of cell proliferation and morphological changes","volume":"11","author":"Kim","year":"1995"},{"key":"b56-0280008","series-title":"Trends Genet","first-page":"84","article-title":"Making of a Schwann","volume":"12","author":"Kioussi","year":"1996"},{"key":"b57-0280008","series-title":"Genes Chromosomes Cancer","first-page":"283","article-title":"Loss of NF1 allele in Schwann cells but not in fibroblasts derived from an NF1-associated neurofibroma","volume":"24","author":"Kluwe","year":"1999"},{"key":"b58-0280008","series-title":"Cancer Genet Cytogenet","first-page":"113","article-title":"Losses in chromosomes 17, 19, and 22q in neurofibromatosis type 1 and sporadic neurofibromas: a comparative genomic hybridization analysis","volume":"136","author":"Koga","year":"2002"},{"key":"b59-0280008","series-title":"Neurofibromatosis: Phenotype, Natural History, and Pathogenesis","first-page":"142","article-title":"Neurofibromas and malignant tumors of the peripheral nerve sheath","author":"Korf","year":"1999"},{"key":"b60-0280008","series-title":"Development","first-page":"4359","article-title":"Neurofibromin modulation of ras activity is required for normal endocardial-mesenchymal transformation in the developing heart","volume":"125","author":"Lakkis","year":"1998"},{"key":"b61-0280008","series-title":"Cell Stem Cell","first-page":"453","article-title":"Cell of origin and microenvironment contribution for NF1-associated dermal neurofibromas","volume":"4","author":"Le","year":"2009"},{"key":"b62-0280008","series-title":"J Neurooncol","first-page":"101","article-title":"Growth of human acoustic neuromas, neurofibromas and schwannomas in the subrenal capsule and sciatic nerve of the nude mouse","volume":"14","author":"Lee","year":"1992"},{"key":"b63-0280008","series-title":"Genes Chromosomes Cancer","first-page":"250","article-title":"TP53 mutations are frequent in malignant NF1 tumors","volume":"10","author":"Legius","year":"1994"},{"key":"b64-0280008","series-title":"Arch Dermatol","first-page":"908","article-title":"Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1: a clinicopathologic and molecular study of 17 patients","volume":"137","author":"Leroy","year":"2001"},{"key":"b65-0280008","series-title":"Pediatr Dev Pathol","first-page":"377","article-title":"p53 and Ki-67 proliferating cell nuclear antigen in benign and malignant peripheral nerve sheath tumors in children","volume":"2","author":"Liapis","year":"1999"},{"key":"b66-0280008","series-title":"Cancer","first-page":"2013","article-title":"p53 mutation as the second event in juvenile chronic myelogenous leukemia in a patient with neurofibromatosis type 1","volume":"80","author":"Luria","year":"1997"},{"key":"b67-0280008","series-title":"Genomics","first-page":"672","article-title":"A yeast artificial chromosome contig encompassing the type 1 neurofibromatosis gene","volume":"13","author":"Marchuk","year":"1992"},{"key":"b68-0280008","series-title":"Cell","first-page":"843","article-title":"The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21","volume":"63","author":"Martin","year":"1990"},{"key":"b69-0280008","series-title":"Oncogene","first-page":"97","article-title":"The angiogenic factor midkine is aberrantly expressed in NF1-deficient Schwann cells and is a mitogen for neurofibroma-derived cells","volume":"20","author":"Mashour","year":"2001"},{"key":"b70-0280008","series-title":"Cancer Cell","first-page":"44","article-title":"Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis","volume":"16","author":"McGillicuddy","year":"2009"},{"key":"b71-0280008","series-title":"Cancer Cell","first-page":"408","article-title":"Thinking beyond the tumor cell: Nf1 haploinsufficiency in the tumor environment","volume":"1","author":"McLaughlin","year":"2002"},{"key":"b72-0280008","series-title":"Proc Natl Acad Sci U S A","first-page":"5435","article-title":"Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis","volume":"87","author":"Menon","year":"1990"},{"key":"b73-0280008","series-title":"Hum Mutat","first-page":"541","article-title":"Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects","volume":"15","author":"Messiaen","year":"2000"},{"key":"b74-0280008","series-title":"J Genet Genomics","first-page":"355","article-title":"Efficacy of combined inhibition of mTOR and ERK\/MAPK pathways in treating a tuberous sclerosis complex cell model","volume":"36","author":"Mi","year":"2009"},{"key":"b75-0280008","series-title":"BMC Med Genet","first-page":"88","article-title":"Identification of a region required for TSC1 stability by functional analysis of TSC1 missense mutations found in individuals with tuberous sclerosis complex","volume":"10","author":"Mozaffari","year":"2009"},{"key":"b76-0280008","series-title":"Clin Exp Metastasis","first-page":"303","article-title":"Differences in proliferation and invasion by normal, transformed and NF1 Schwann cell cultures are influenced by matrix metalloproteinase expression","volume":"13","author":"Muir","year":"1995"},{"key":"b77-0280008","series-title":"Am J Pathol","first-page":"501","article-title":"Tumorigenic properties of neurofibromin-deficient neurofibroma Schwann cells","volume":"158","author":"Muir","year":"2001"},{"key":"b78-0280008","series-title":"Nature","first-page":"705","article-title":"Mutations in the p53 gene occur in diverse human tumour types","volume":"342","author":"Nigro","year":"1989"},{"key":"b79-0280008","series-title":"Science","first-page":"1807","article-title":"An integrated genomic analysis of human glioblastoma multiforme","volume":"321","author":"Parsons","year":"2008"},{"key":"b80-0280008","series-title":"Lab Invest","first-page":"760","article-title":"Cellular differentiation and expression of matrix genes in type 1 neurofibromatosis","volume":"59","author":"Peltonen","year":"1988"},{"key":"b81-0280008","series-title":"J Neurosurg","first-page":"35","article-title":"Electron microscopy of the lemmocyte in peripheral nerve tumors (neurolemmomas)","volume":"25","author":"Pineda","year":"1966"},{"key":"b82-0280008","series-title":"Genes Chromosomes Cancer","first-page":"425","article-title":"Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1","volume":"28","author":"Rasmussen","year":"2000"},{"key":"b83-0280008","series-title":"Ann Neurol","first-page":"298","article-title":"Mitogen accumulation in von Recklinghausen neurofibromatosis","volume":"27","author":"Ratner","year":"1990"},{"key":"b84-0280008","series-title":"Mutat Res","first-page":"185","article-title":"Homonucleotide tracts, short repeats and CpG\/CpNpG motifs are frequent sites for heterogeneous mutations in the neurofibromatosis type 1 (NF1) tumour-suppressor gene","volume":"373","author":"Rodenhiser","year":"1997"},{"key":"b85-0280008","series-title":"Ital J Orthop Traumatol","first-page":"237","article-title":"The ultrastructure of schwannoma and neurofibroma of the peripheral nerves","volume":"17","author":"Sanguinetti","year":"1991"},{"key":"b86-0280008","series-title":"Nat Genet","first-page":"110","article-title":"Identification of NF1 mutations in both alleles of a dermal neurofibroma","volume":"14","author":"Sawada","year":"1996"},{"key":"b87-0280008","series-title":"Hum Genet","first-page":"416","article-title":"Somatic NF1 mutational spectrum in benign neurofibromas: mRNA splice defects are common among point mutations","volume":"108","author":"Serra","year":"2001"},{"key":"b88-0280008","series-title":"Hum Mol Genet","first-page":"3055","article-title":"Schwann cells harbor the somatic NF1 mutation in neurofibromas: evidence of two different Schwann cell subpopulations","volume":"9","author":"Serra","year":"2000"},{"key":"b89-0280008","series-title":"J Cell Biol","first-page":"645","article-title":"Angiogenic and invasive properties of neurofibroma Schwann cells","volume":"111","author":"Sheela","year":"1990"},{"key":"b90-0280008","series-title":"Am J Pathol","first-page":"261","article-title":"S-100 protein in softtissue tumors derived from Schwann cells and melanocytes","volume":"106","author":"Stefansson","year":"1982"},{"key":"b91-0280008","series-title":"Cell","first-page":"447","article-title":"Conspiracy theory: RAS and RAF do not act alone","volume":"95","author":"Sternberg","year":"1998"},{"key":"b92-0280008","series-title":"Curr Opin Genet Dev","first-page":"230","article-title":"The RASopathies: developmental syndromes of Ras\/MAPK pathway dysregulation","volume":"19","author":"Tidyman","year":"2009"},{"key":"b93-0280008","series-title":"Science","first-page":"542","article-title":"A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants","volume":"238","author":"Trahey","year":"1987"},{"key":"b94-0280008","series-title":"J Med Genet","first-page":"81","article-title":"Longitudinal study of neurofibromatosis 1 associated plexiform neurofibromas","volume":"46","author":"Tucker","year":"2009"},{"key":"b95-0280008","series-title":"Hum Mutat","first-page":"134","article-title":"Characterization of the somatic mutational spectrum of the neurofibromatosis type 1 (NF1) gene in neurofibromatosis patients with benign and malignant tumors","volume":"23","author":"Upadhyaya","year":"2004"},{"key":"b96-0280008","series-title":"J Med Genet","first-page":"706","article-title":"Characterisation of germline mutations in the neurofibromatosis type 1 (NF1) gene","volume":"32","author":"Upadhyaya","year":"1995"},{"key":"b97-0280008","series-title":"Cell","first-page":"187","article-title":"Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus","volume":"62","author":"Viskochil","year":"1990"},{"key":"b98-0280008","series-title":"Neurofibromatosis: Phenotype, Natural History, and Pathogenesis","first-page":"119","article-title":"The structure and function of the NF1 gene: molecular pathophysiology","author":"Viskochil","year":"1999"},{"key":"b99-0280008","series-title":"J Biol Chem","first-page":"5241","article-title":"A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)","volume":"269","author":"Vlahos","year":"1994"},{"key":"b100-0280008","series-title":"Science","first-page":"2176","article-title":"Mouse tumor model for neurofibromatosis type 1","volume":"286","author":"Vogel","year":"1999"},{"key":"b101-0280008","series-title":"Pathology and Genetics: Tumours of the Nervous System","first-page":"216","article-title":"Familial tumour syndromes involving the nervous system","author":"von Deimling","year":"2000"},{"key":"b102-0280008","series-title":"Cancer","first-page":"699","article-title":"Ultrastructure of benign peripheral nerve sheath tumors","volume":"19","author":"Waggener","year":"1966"},{"key":"b103-0280008","series-title":"Science","first-page":"181","article-title":"Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients","volume":"249","author":"Wallace","year":"1990"},{"key":"b104-0280008","series-title":"Am J Med Genet","first-page":"14","article-title":"Hyperactive Ras as a therapeutic target in neurofibromatosis type 1","volume":"89","author":"Weiss","year":"1999"},{"key":"b105-0280008","series-title":"Am J Med Genet","first-page":"23","article-title":"Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis","volume":"89","author":"Woodruff","year":"1999"},{"key":"b106-0280008","series-title":"Cell","first-page":"835","article-title":"The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae","volume":"63","author":"Xu","year":"1990"},{"key":"b107-0280008","series-title":"Cell","first-page":"599","article-title":"The neurofibromatosis type 1 gene encodes a protein related to GAP","volume":"62","author":"Xu","year":"1990"},{"key":"b108-0280008","series-title":"Cancer Res","first-page":"3569","article-title":"Farnesyltransferase inhibitors block the neurofibromatosis type I (NF1) malignant phenotype","volume":"55","author":"Yan","year":"1995"},{"key":"b109-0280008","series-title":"J Clin Invest","first-page":"1851","article-title":"Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+\/\u2013 mast cells","volume":"112","author":"Yang","year":"2003"},{"key":"b110-0280008","series-title":"Cell","first-page":"437","article-title":"Nf1-dependent tumors require a microenvironment containing Nf1+\/\u2013 and c-kit-dependent bone marrow","volume":"135","author":"Yang","year":"2008"},{"key":"b111-0280008","series-title":"Science","first-page":"2003","article-title":"Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor","volume":"267","author":"Yao","year":"1995"},{"key":"b112-0280008","series-title":"Glia","first-page":"1239","article-title":"Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)-regulated glial proliferation","volume":"57","author":"Yeh","year":"2009"},{"key":"b113-0280008","series-title":"Cancer Cell","first-page":"117","article-title":"Induction of abnormal proliferation by nonmyelinating schwann cells triggers neurofibroma formation","volume":"13","author":"Zheng","year":"2008"},{"key":"b114-0280008","series-title":"Science","first-page":"920","article-title":"Neurofibromas in NF1: Schwann cell origin and role of tumor environment","volume":"296","author":"Zhu","year":"2002"},{"key":"b1-0280008","series-title":"J Biol Chem","first-page":"16409","article-title":"Structural differences in the minimal catalytic domains of the GTPase-activating proteins p120GAP and neurofibromin","volume":"271","author":"Ahmadian","year":"1996"},{"key":"b2-0280008","series-title":"Expert Rev Neurother","first-page":"535","article-title":"Gliomas in patients with neurofibromatosis type 1","volume":"9","author":"Albers","year":"2009"},{"key":"b3-0280008","series-title":"J Neurol Sci","first-page":"69","article-title":"Neurofibromatosis xenografts. Contribution to pathogenesis","volume":"74","author":"Appenzeller","year":"1986"},{"key":"b4-0280008","series-title":"Hum Mol Genet","first-page":"237","article-title":"Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1","volume":"9","author":"Ars","year":"2000"},{"key":"b5-0280008","series-title":"Cancer Res","first-page":"8573","article-title":"Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity","volume":"63","author":"Bajenaru","year":"2003"},{"key":"b6-0280008","series-title":"Cell","first-page":"851","article-title":"The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins","volume":"63","author":"Ballester","year":"1990"},{"key":"b7-0280008","series-title":"Nature","first-page":"713","article-title":"Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients","volume":"356","author":"Basu","year":"1992"},{"key":"b8-0280008","series-title":"Biochim Biophys Acta","first-page":"43","article-title":"Neurofibromatosis type 1 and Ras-mediated signaling: filling in the GAPs","volume":"1242","author":"Bernards","year":"1995"},{"key":"b9-0280008","series-title":"DNA Cell Biol","first-page":"727","article-title":"Complete human NF1 cDNA sequence: two alternatively spliced mRNAs and absence of expression in a neuroblastoma line","volume":"11","author":"Bernards","year":"1992"},{"key":"b10-0280008","series-title":"Int J Cancer","article-title":"Preclinical in vivo evaluation of rapamycin in human malignant peripheral nerve sheath explant xenograft","author":"Bhola","year":"2009"},{"key":"b11-0280008","series-title":"Lab Invest","first-page":"833","article-title":"Rb and TP53 pathway alterations in sporadic and NF1-related malignant peripheral nerve sheath tumors","volume":"81","author":"Birindelli","year":"2001"},{"key":"b12-0280008","series-title":"Mol Cell Biol","first-page":"3964","article-title":"Ral overactivation in malignant peripheral nerve sheath tumors","volume":"29","author":"Bodempudi","year":"2009"},{"key":"b13-0280008","series-title":"Nat Genet","first-page":"144","article-title":"Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells","volume":"12","author":"Bollag","year":"1996"},{"key":"b14-0280008","series-title":"Nature","first-page":"576","article-title":"Differential regulation of rasGAP and neurofibromatosis gene product activities","volume":"351","author":"Bollag","year":"1991"},{"key":"b15-0280008","series-title":"Genes Dev","first-page":"1019","article-title":"Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues","volume":"8","author":"Brannan","year":"1994"},{"key":"b16-0280008","series-title":"Lancet Oncol","first-page":"508","article-title":"Mechanisms in the pathogenesis of malignant tumours in neurofibromatosis type 1","volume":"10","author":"Brems","year":"2009"},{"key":"b17-0280008","series-title":"Nature","first-page":"291","article-title":"Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway","volume":"347","author":"Buchberg","year":"1990"},{"key":"b18-0280008","series-title":"Surgical Pathology of the Nervous System and Its Coverings","author":"Burger","year":"2002"},{"key":"b19-0280008","series-title":"Cell","first-page":"193","article-title":"A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations","volume":"62","author":"Cawthon","year":"1990"},{"key":"b20-0280008","series-title":"Science","first-page":"2172","article-title":"Mouse models of tumor development in neurofibromatosis type 1","volume":"286","author":"Cichowski","year":"1999"},{"key":"b21-0280008","series-title":"Science","first-page":"1332","article-title":"Reovirus therapy of tumors with activated Ras pathway","volume":"282","author":"Coffey","year":"1998"},{"key":"b22-0280008","series-title":"Nature","first-page":"860","article-title":"Inflammation and cancer","volume":"420","author":"Coussens","year":"2002"},{"key":"b23-0280008","series-title":"J Exp Med","first-page":"F23","article-title":"Inflammatory cells and cancer: think different!","volume":"193","author":"Coussens","year":"2001"},{"key":"b24-0280008","series-title":"Neuron","first-page":"415","article-title":"The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes","volume":"8","author":"Daston","year":"1992"},{"key":"b25-0280008","series-title":"Cell","first-page":"265","article-title":"Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis","volume":"69","author":"DeClue","year":"1992"},{"key":"b26-0280008","series-title":"J Med Genet","first-page":"695","article-title":"Clinical and molecular aspects of RAS related disorders","volume":"45","author":"Denayer","year":"2008"},{"key":"b27-0280008","series-title":"Curr Opin Genet Dev","first-page":"49","article-title":"Ras signalling and apoptosis","volume":"8","author":"Downward","year":"1998"},{"key":"b28-0280008","series-title":"Proc Natl Acad Sci U S A","first-page":"7686","article-title":"A synthetic inhibitor of the mitogen-activated protein kinase cascade","volume":"92","author":"Dudley","year":"1995"},{"key":"b29-0280008","series-title":"Dev Biol","first-page":"235","article-title":"Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4","volume":"188","author":"Dunn","year":"1997"},{"key":"b30-0280008","series-title":"J Intellect Disabil Res","first-page":"838","article-title":"From mTOR to cognition: molecular and cellular mechanisms of cognitive impairments in tuberous sclerosis","volume":"53","author":"Ehninger","year":"2009"},{"key":"b31-0280008","series-title":"Am J Hum Genet","first-page":"393","article-title":"Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1","volume":"66","author":"Eisenbarth","year":"2000"},{"key":"b32-0280008","series-title":"Am J Med Genet","first-page":"325","article-title":"Neurofibromatosis type I (NFI) in Israeli families: linkage analysis as a diagnostic tool","volume":"53","author":"Elyakim","year":"1994"},{"key":"b33-0280008","series-title":"Am J Hum Genet","first-page":"790","article-title":"Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain","volume":"66","author":"Fahsold","year":"2000"},{"key":"b34-0280008","series-title":"J Biol Chem","first-page":"18623","article-title":"Identification of a novel inhibitor of mitogen-activated protein kinase kinase","volume":"273","author":"Favata","year":"1998"},{"key":"b35-0280008","series-title":"Neurofibromatosis: Phenotype, Natural History, and Pathogenesis","first-page":"110","article-title":"Clinical genetics","author":"Friedman","year":"1999"},{"key":"b36-0280008","series-title":"Eur J Neurosci","first-page":"77","article-title":"Fibroblast growth factors and insulin growth factors combine to promote survival of rat Schwann cell precursors without induction of DNA synthesis","volume":"7","author":"Gavrilovic","year":"1995"},{"key":"b37-0280008","series-title":"Genes Chromosomes Cancer","first-page":"62","article-title":"Molecular and cytogenetic analysis of tumors in von Recklinghausen neurofibromatosis","volume":"3","author":"Glover","year":"1991"},{"key":"b38-0280008","series-title":"Neurosurgery","first-page":"1","article-title":"Molecular, genetic, and cellular pathogenesis of neurofibromas and surgical implications","volume":"58","author":"Gottfried","year":"2006"},{"key":"b39-0280008","series-title":"Oncogene","first-page":"507","article-title":"Ras-GTP levels are elevated in human NF1 peripheral nerve tumors","volume":"12","author":"Guha","year":"1996"},{"key":"b40-0280008","series-title":"Cell Growth Differ","first-page":"315","article-title":"Expression of the neurofibromatosis 1 (NF1) isoforms in developing and adult rat tissues","volume":"6","author":"Gutmann","year":"1995"},{"key":"b41-0280008","series-title":"Cell","first-page":"57","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000"},{"key":"b42-0280008","series-title":"Cancer Res","first-page":"1520","article-title":"Preclinical cancer therapy in a mouse model of neurofibromatosis-1 optic glioma","volume":"68","author":"Hegedus","year":"2008"},{"key":"b43-0280008","series-title":"Neurosurgery","first-page":"685","article-title":"Using mice to decipher the molecular genetics of brain tumors","volume":"53","author":"Hesselager","year":"2003"},{"key":"b44-0280008","series-title":"Cancer Res","first-page":"6107","article-title":"Signaling events downstream of mammalian target of rapamycin complex 2 are attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor suppressors","volume":"69","author":"Huang","year":"2009"},{"key":"b45-0280008","series-title":"J Exp Med","first-page":"181","article-title":"Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo","volume":"191","author":"Ingram","year":"2000"},{"key":"b46-0280008","series-title":"Nat Genet","first-page":"353","article-title":"Tumour predisposition in mice heterozygous for a targeted mutation in Nf1","volume":"7","author":"Jacks","year":"1994"},{"key":"b47-0280008","series-title":"Nature","first-page":"558","article-title":"Paternal origin of new mutations in von Recklinghausen neurofibromatosis","volume":"343","author":"Jadayel","year":"1990"},{"key":"b48-0280008","series-title":"Microsc Res Tech","first-page":"393","article-title":"Origin and early development of Schwann cells","volume":"41","author":"Jessen","year":"1998"},{"key":"b49-0280008","series-title":"Cancer Genet Cytogenet","first-page":"138","article-title":"Cytogenetic analysis of soft tissue sarcomas. Recurrent chromosome abnormalities in malignant peripheral nerve sheath tumors (MPNST)","volume":"78","author":"Jhanwar","year":"1994"},{"key":"b50-0280008","series-title":"Curr Biol","first-page":"56","article-title":"TORC1 is essential for NF1-associated malignancies","volume":"18","author":"Johannessen","year":"2008"},{"key":"b51-0280008","series-title":"Proc Natl Acad Sci U S A","first-page":"8573","article-title":"The NF1 tumor suppressor critically regulates TSC2 and mTOR","volume":"102","author":"Johannessen","year":"2005"},{"key":"b52-0280008","series-title":"J Med Genet","first-page":"44","article-title":"A search for evidence of somatic mutations in the NF1 gene","volume":"37","author":"John","year":"2000"},{"key":"b53-0280008","series-title":"Cancer Cell","first-page":"129","article-title":"The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells","volume":"13","author":"Joseph","year":"2008"},{"key":"b54-0280008","series-title":"Expert Rev Mol Med","first-page":"e30","article-title":"Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways","volume":"11","author":"Katz","year":"2009"},{"key":"b55-0280008","series-title":"Oncogene","first-page":"325","article-title":"Schwann cells from neurofibromin deficient mice exhibit activation of p21ras, inhibition of cell proliferation and morphological changes","volume":"11","author":"Kim","year":"1995"},{"key":"b56-0280008","series-title":"Trends Genet","first-page":"84","article-title":"Making of a Schwann","volume":"12","author":"Kioussi","year":"1996"},{"key":"b57-0280008","series-title":"Genes Chromosomes Cancer","first-page":"283","article-title":"Loss of NF1 allele in Schwann cells but not in fibroblasts derived from an NF1-associated neurofibroma","volume":"24","author":"Kluwe","year":"1999"},{"key":"b58-0280008","series-title":"Cancer Genet Cytogenet","first-page":"113","article-title":"Losses in chromosomes 17, 19, and 22q in neurofibromatosis type 1 and sporadic neurofibromas: a comparative genomic hybridization analysis","volume":"136","author":"Koga","year":"2002"},{"key":"b59-0280008","series-title":"Neurofibromatosis: Phenotype, Natural History, and Pathogenesis","first-page":"142","article-title":"Neurofibromas and malignant tumors of the peripheral nerve sheath","author":"Korf","year":"1999"},{"key":"b60-0280008","series-title":"Development","first-page":"4359","article-title":"Neurofibromin modulation of ras activity is required for normal endocardial-mesenchymal transformation in the developing heart","volume":"125","author":"Lakkis","year":"1998"},{"key":"b61-0280008","series-title":"Cell Stem Cell","first-page":"453","article-title":"Cell of origin and microenvironment contribution for NF1-associated dermal neurofibromas","volume":"4","author":"Le","year":"2009"},{"key":"b62-0280008","series-title":"J Neurooncol","first-page":"101","article-title":"Growth of human acoustic neuromas, neurofibromas and schwannomas in the subrenal capsule and sciatic nerve of the nude mouse","volume":"14","author":"Lee","year":"1992"},{"key":"b63-0280008","series-title":"Genes Chromosomes Cancer","first-page":"250","article-title":"TP53 mutations are frequent in malignant NF1 tumors","volume":"10","author":"Legius","year":"1994"},{"key":"b64-0280008","series-title":"Arch Dermatol","first-page":"908","article-title":"Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1: a clinicopathologic and molecular study of 17 patients","volume":"137","author":"Leroy","year":"2001"},{"key":"b65-0280008","series-title":"Pediatr Dev Pathol","first-page":"377","article-title":"p53 and Ki-67 proliferating cell nuclear antigen in benign and malignant peripheral nerve sheath tumors in children","volume":"2","author":"Liapis","year":"1999"},{"key":"b66-0280008","series-title":"Cancer","first-page":"2013","article-title":"p53 mutation as the second event in juvenile chronic myelogenous leukemia in a patient with neurofibromatosis type 1","volume":"80","author":"Luria","year":"1997"},{"key":"b67-0280008","series-title":"Genomics","first-page":"672","article-title":"A yeast artificial chromosome contig encompassing the type 1 neurofibromatosis gene","volume":"13","author":"Marchuk","year":"1992"},{"key":"b68-0280008","series-title":"Cell","first-page":"843","article-title":"The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21","volume":"63","author":"Martin","year":"1990"},{"key":"b69-0280008","series-title":"Oncogene","first-page":"97","article-title":"The angiogenic factor midkine is aberrantly expressed in NF1-deficient Schwann cells and is a mitogen for neurofibroma-derived cells","volume":"20","author":"Mashour","year":"2001"},{"key":"b70-0280008","series-title":"Cancer Cell","first-page":"44","article-title":"Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis","volume":"16","author":"McGillicuddy","year":"2009"},{"key":"b71-0280008","series-title":"Cancer Cell","first-page":"408","article-title":"Thinking beyond the tumor cell: Nf1 haploinsufficiency in the tumor environment","volume":"1","author":"McLaughlin","year":"2002"},{"key":"b72-0280008","series-title":"Proc Natl Acad Sci U S A","first-page":"5435","article-title":"Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis","volume":"87","author":"Menon","year":"1990"},{"key":"b73-0280008","series-title":"Hum Mutat","first-page":"541","article-title":"Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects","volume":"15","author":"Messiaen","year":"2000"},{"key":"b74-0280008","series-title":"J Genet Genomics","first-page":"355","article-title":"Efficacy of combined inhibition of mTOR and ERK\/MAPK pathways in treating a tuberous sclerosis complex cell model","volume":"36","author":"Mi","year":"2009"},{"key":"b75-0280008","series-title":"BMC Med Genet","first-page":"88","article-title":"Identification of a region required for TSC1 stability by functional analysis of TSC1 missense mutations found in individuals with tuberous sclerosis complex","volume":"10","author":"Mozaffari","year":"2009"},{"key":"b76-0280008","series-title":"Clin Exp Metastasis","first-page":"303","article-title":"Differences in proliferation and invasion by normal, transformed and NF1 Schwann cell cultures are influenced by matrix metalloproteinase expression","volume":"13","author":"Muir","year":"1995"},{"key":"b77-0280008","series-title":"Am J Pathol","first-page":"501","article-title":"Tumorigenic properties of neurofibromin-deficient neurofibroma Schwann cells","volume":"158","author":"Muir","year":"2001"},{"key":"b78-0280008","series-title":"Nature","first-page":"705","article-title":"Mutations in the p53 gene occur in diverse human tumour types","volume":"342","author":"Nigro","year":"1989"},{"key":"b79-0280008","series-title":"Science","first-page":"1807","article-title":"An integrated genomic analysis of human glioblastoma multiforme","volume":"321","author":"Parsons","year":"2008"},{"key":"b80-0280008","series-title":"Lab Invest","first-page":"760","article-title":"Cellular differentiation and expression of matrix genes in type 1 neurofibromatosis","volume":"59","author":"Peltonen","year":"1988"},{"key":"b81-0280008","series-title":"J Neurosurg","first-page":"35","article-title":"Electron microscopy of the lemmocyte in peripheral nerve tumors (neurolemmomas)","volume":"25","author":"Pineda","year":"1966"},{"key":"b82-0280008","series-title":"Genes Chromosomes Cancer","first-page":"425","article-title":"Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1","volume":"28","author":"Rasmussen","year":"2000"},{"key":"b83-0280008","series-title":"Ann Neurol","first-page":"298","article-title":"Mitogen accumulation in von Recklinghausen neurofibromatosis","volume":"27","author":"Ratner","year":"1990"},{"key":"b84-0280008","series-title":"Mutat Res","first-page":"185","article-title":"Homonucleotide tracts, short repeats and CpG\/CpNpG motifs are frequent sites for heterogeneous mutations in the neurofibromatosis type 1 (NF1) tumour-suppressor gene","volume":"373","author":"Rodenhiser","year":"1997"},{"key":"b85-0280008","series-title":"Ital J Orthop Traumatol","first-page":"237","article-title":"The ultrastructure of schwannoma and neurofibroma of the peripheral nerves","volume":"17","author":"Sanguinetti","year":"1991"},{"key":"b86-0280008","series-title":"Nat Genet","first-page":"110","article-title":"Identification of NF1 mutations in both alleles of a dermal neurofibroma","volume":"14","author":"Sawada","year":"1996"},{"key":"b87-0280008","series-title":"Hum Genet","first-page":"416","article-title":"Somatic NF1 mutational spectrum in benign neurofibromas: mRNA splice defects are common among point mutations","volume":"108","author":"Serra","year":"2001"},{"key":"b88-0280008","series-title":"Hum Mol Genet","first-page":"3055","article-title":"Schwann cells harbor the somatic NF1 mutation in neurofibromas: evidence of two different Schwann cell subpopulations","volume":"9","author":"Serra","year":"2000"},{"key":"b89-0280008","series-title":"J Cell Biol","first-page":"645","article-title":"Angiogenic and invasive properties of neurofibroma Schwann cells","volume":"111","author":"Sheela","year":"1990"},{"key":"b90-0280008","series-title":"Am J Pathol","first-page":"261","article-title":"S-100 protein in softtissue tumors derived from Schwann cells and melanocytes","volume":"106","author":"Stefansson","year":"1982"},{"key":"b91-0280008","series-title":"Cell","first-page":"447","article-title":"Conspiracy theory: RAS and RAF do not act alone","volume":"95","author":"Sternberg","year":"1998"},{"key":"b92-0280008","series-title":"Curr Opin Genet Dev","first-page":"230","article-title":"The RASopathies: developmental syndromes of Ras\/MAPK pathway dysregulation","volume":"19","author":"Tidyman","year":"2009"},{"key":"b93-0280008","series-title":"Science","first-page":"542","article-title":"A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants","volume":"238","author":"Trahey","year":"1987"},{"key":"b94-0280008","series-title":"J Med Genet","first-page":"81","article-title":"Longitudinal study of neurofibromatosis 1 associated plexiform neurofibromas","volume":"46","author":"Tucker","year":"2009"},{"key":"b95-0280008","series-title":"Hum Mutat","first-page":"134","article-title":"Characterization of the somatic mutational spectrum of the neurofibromatosis type 1 (NF1) gene in neurofibromatosis patients with benign and malignant tumors","volume":"23","author":"Upadhyaya","year":"2004"},{"key":"b96-0280008","series-title":"J Med Genet","first-page":"706","article-title":"Characterisation of germline mutations in the neurofibromatosis type 1 (NF1) gene","volume":"32","author":"Upadhyaya","year":"1995"},{"key":"b97-0280008","series-title":"Cell","first-page":"187","article-title":"Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus","volume":"62","author":"Viskochil","year":"1990"},{"key":"b98-0280008","series-title":"Neurofibromatosis: Phenotype, Natural History, and Pathogenesis","first-page":"119","article-title":"The structure and function of the NF1 gene: molecular pathophysiology","author":"Viskochil","year":"1999"},{"key":"b99-0280008","series-title":"J Biol Chem","first-page":"5241","article-title":"A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)","volume":"269","author":"Vlahos","year":"1994"},{"key":"b100-0280008","series-title":"Science","first-page":"2176","article-title":"Mouse tumor model for neurofibromatosis type 1","volume":"286","author":"Vogel","year":"1999"},{"key":"b101-0280008","series-title":"Pathology and Genetics: Tumours of the Nervous System","first-page":"216","article-title":"Familial tumour syndromes involving the nervous system","author":"von Deimling","year":"2000"},{"key":"b102-0280008","series-title":"Cancer","first-page":"699","article-title":"Ultrastructure of benign peripheral nerve sheath tumors","volume":"19","author":"Waggener","year":"1966"},{"key":"b103-0280008","series-title":"Science","first-page":"181","article-title":"Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients","volume":"249","author":"Wallace","year":"1990"},{"key":"b104-0280008","series-title":"Am J Med Genet","first-page":"14","article-title":"Hyperactive Ras as a therapeutic target in neurofibromatosis type 1","volume":"89","author":"Weiss","year":"1999"},{"key":"b105-0280008","series-title":"Am J Med Genet","first-page":"23","article-title":"Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis","volume":"89","author":"Woodruff","year":"1999"},{"key":"b106-0280008","series-title":"Cell","first-page":"835","article-title":"The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae","volume":"63","author":"Xu","year":"1990"},{"key":"b107-0280008","series-title":"Cell","first-page":"599","article-title":"The neurofibromatosis type 1 gene encodes a protein related to GAP","volume":"62","author":"Xu","year":"1990"},{"key":"b108-0280008","series-title":"Cancer Res","first-page":"3569","article-title":"Farnesyltransferase inhibitors block the neurofibromatosis type I (NF1) malignant phenotype","volume":"55","author":"Yan","year":"1995"},{"key":"b109-0280008","series-title":"J Clin Invest","first-page":"1851","article-title":"Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+\/\u2013 mast cells","volume":"112","author":"Yang","year":"2003"},{"key":"b110-0280008","series-title":"Cell","first-page":"437","article-title":"Nf1-dependent tumors require a microenvironment containing Nf1+\/\u2013 and c-kit-dependent bone marrow","volume":"135","author":"Yang","year":"2008"},{"key":"b111-0280008","series-title":"Science","first-page":"2003","article-title":"Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor","volume":"267","author":"Yao","year":"1995"},{"key":"b112-0280008","series-title":"Glia","first-page":"1239","article-title":"Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)-regulated glial proliferation","volume":"57","author":"Yeh","year":"2009"},{"key":"b113-0280008","series-title":"Cancer Cell","first-page":"117","article-title":"Induction of abnormal proliferation by nonmyelinating schwann cells triggers neurofibroma formation","volume":"13","author":"Zheng","year":"2008"},{"key":"b114-0280008","series-title":"Science","first-page":"920","article-title":"Neurofibromas in NF1: Schwann cell origin and role of tumor environment","volume":"296","author":"Zhu","year":"2002"}],"container-title":["Neurosurgical Focus"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/neurosurg-focus\/28\/1\/article-pE8.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/neurosurg-focus\/28\/1\/article-pE8.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/neurosurg-focus\/28\/1\/article-pE8.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:17:40Z","timestamp":1780733860000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/neurosurg-focus\/28\/1\/article-pE8.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1]]},"references-count":228,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3171\/2009.11.focus09221","relation":{},"ISSN":["1092-0684"],"issn-type":[{"value":"1092-0684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,1]]}}}