Neurofibromatosis

Annual Review of Pathology

Volumn 2, Issue , 2007, Pages 191-216

  McClatchey, Andrea I ^a,b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Ezrin; Membrane organization; Merlin Schwannomin; Moesin (the ERM proteins); Neurofibromin; Peripheral nerve sheath tumor; Radixin; Ras signaling; Schwannoma

Indexed keywords

EZRIN; GROWTH FACTOR RECEPTOR; MERLIN; MOESIN; NEUROFIBROMIN; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RADIXIN;

CARCINOGENESIS; CLINICAL FEATURE; EXPERIMENTAL MODEL; FAMILIAL CANCER; GENE; GENE EXPRESSION; GLIOMA; HUMAN; MYELOID LEUKEMIA; NERVOUS SYSTEM TUMOR; NEURILEMOMA; NEUROFIBROMATOSIS; NF2 GENE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION;

EID: 33947429718     PISSN: 15534006     EISSN: 15534014     Source Type: Book Series    
DOI: 10.1146/annurev.pathol.2.010506.091940     Document Type: Review

References (148)

1. Friedman JM, Gutmann DH, Riccardi VM, eds. 1999. Neurofibromatosis: Phenotype, Natural History, and Pathogenesis. Baltimore: Johns Hopkins Univ. Press. 400 pp. 3rd ed.
2. Huson S, Hughes R. 1994. The Neurofibromatoses: A Pathogenetic and Clinical Overview. London: Chapman & Hall Medical. 487 pp.
3. Korf BR, Rubenstein AE. 2005. Neurofibromatosis: A Handbook for Patients, Families, and Health Care Professionals. New York: Thieme Med. Publ. 253 pp.
4. MacCollin M, Chiocca EA, Evans DG, Friedman JM, Horvitz R, et al. 2005. Diagnostic criteria for schwannomatosis. Neurology 64:1838-45
5. von Recklinghausen F. 1882. Ueber die Multiplen Fibrome der Haut und ihre Beziehung zu den Multiplen Neuromen. Berlin: Hirschwald 138 pp.
6. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, et al. 1997. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278:51-57
7. Perry A, Roth KA, Banerjee R, Fuller CE, Gutmann DH. 2001. NF1 deletions in S-100 protein-positive and negative cells of sporadic and neurofibromatosis 1 (NF1)-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors. Am. J. Pathol. 159:57-61
8. Side L, Taylor B, Cayouette M, Conner E, Thompson P, et al. 1997. Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders. N. Engl. J. Med. 336:1713-20
9. Zhu Y, Ghosh P, Charnay P, Burns DK, Parada LF. 2002. Neurofibromas in NF1: Schwann cell origin and role of tumor environment. Science 296:920-22
10. Bajenaru ML, Hernandez MR, Perry A, Zhu Y, Parada LF, et al. 2003. Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity. Canc. Res. 63:8573-77
11. MacCollin M, Willett C, Heinrich B, Jacoby LB, Acierno JSJ, et al. 2003. Familial schwannomatosis: exclusion of the NF2 locus as the germline event. Neurology 60:1968-74
12. Cawthon RM, Weiss R, Xu GF, Viskochil D, Culver M, et al. 1990. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 62:193-201
13. Viskochil D, Buchberg AM, Xu G, Cawthon RM, Stevens J, et al. 1990. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 62:187-92
14. Wallace MR, Marchuk DA, Andersen LB, Letcher R, Odeh HM, et al. 1990. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249:181-86
15. Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, et al. 1993. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72(5):791-800
16. Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, et al. 1993. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363:515-21
17. Sekido Y, Pass HI, Bader S, Mew DJ, Christman MF, et al. 1995. Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Canc. Res. 55:1227-31
18. Stemmer-Rachamimov AO, Xu L, Gonzalez-Agosti C, Burwick JA, Pinney D, et al. 1997. Universal absence of merlin, but not other ERM family members, in schwannomas. Am. J. Pathol. 151:1649-54
19. Ruttledge MH, Sarrazin J, Rangaratnam S, Phelan CM, Twist E, et al. 1994. Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nat. Genet. 6:180-84
20. Lomas J, Bello MJ, Arjona D, Alonso ME, Martinez-Glez V, et al. 2005. Genetic and epigenetic alteration of the NF2 gene in sporadic meningiomas. Genes Chromosomes Canc. 42:314-19
21. Bianchi AB, Mitsunaga SI, Cheng JQ, Klein WM, Jhanwar SC, et al. 1995. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc. Natl. Acad. Sci. USA 92:10854-58
22. Thomson SA, Fishbein L, Wallace MR. 2002. NF1 mutations and molecular testing. J. Child Neurol. 17:555-61; discussion 71-2, 646-51
23. Dorschner MO, Sybert VP, Weaver M, Pletcher BA, Stephens K. 2000. NF1 microdeletion breakpoints are clustered at flanking repetitive sequences. Hum. Mol. Genet. 9:35-46
24. Hulsebos TJ, Bijleveld EH, Riegman PH, Smink LJ, Dunham I. 1996. Identification and characterization of NF1-related loci on human chromosomes 22, 14 and 2. Hum. Genet. 98:7-11
25. Wang Q, Montmain G, Ruano E, Upadhyaya M, Dudley S, et al. 2003. Neurofibromatosis type 1 gene as a mutational target in a mismatch repair-deficient cell type. Hum. Genet. 112:117-23
26. Gutmann DH, Winkeler E, Kabbarah O, Hedrick N, Dudley S, et al. 2003. Mlh1 deficiency accelerates myeloid leukemogenesis in neurofibromatosis 1 (Nf1) heterozygous mice. Oncogene 22:4581-85
27. Leppig KA, Kaplan P, Viskochil D, Weaver M, Ortenberg J, Stephens K. 1997. Familial neurofibromatosis 1 microdeletions: cosegregation with distinct facial phenotype and early onset of cutaneous neurofibromata. Am. J. Med. Genet. 73:197-204
28. Easton DF, Ponder MA, Huson SM, Ponder BA. 1993. An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am. J. Hum. Genet. 53:305-13
29. Szudek J, Joe H, Friedman JM. 2002. Analysis of intrafamilial phenotypic variation in neurofibromatosis 1 (NF1). Genet. Epidemiol. 23:150-64
30. Szudek J, Evans DG, Friedman JM. 2003. Patterns of associations of clinical features in neurofibromatosis 1 (NF1). Hum. Genet. 112:289-97
31. Merel P, Hoang-Xuan K, Sanson M, Bijlsma E, Rouleau G, et al. 1995. Screening for germ-line mutations in the NF2 gene. Genes Chromosomes Canc. 12:117-27
32. Kluwe L, Bayer S, Baser ME, Hazim W, Haase W, et al. 1996. Identification of NF2 germ-line mutations and comparison with neurofibromatosis 2 phenotypes. Hum. Genet. 98:534-38
33. Kluwe L, MacCollin M, Tatagiba M, Thomas S, Hazim W, et al. 1998. Phenotypic variability associated with 14 splice-site mutations in the NF2 gene. Am. J. Med. Genet. 77:228-33
34. Parry DM, MacCollin MM, Kaiser-Kupfer MI, Pulaski K, Nicholson HS, et al. 1996. Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities. Am. J. Hum. Genet. 59:529-39
35. Ruttledge MH, Andermann AA, Phelan CM, Claudio JO, Han FY, et al. 1996. Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease. Am. J. Hum. Genet. 59:331-42
36. Evans DG, Trueman L, Wallace A, Collins S, Strachan T. 1998. Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for more severe disease associated with truncating mutations. J. Med. Genet. 35:450-55
37. Evans DG, Wallace AJ, Wu CL, Trueman L, Ramsden RT, Strachan T. 1998. Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis. Am. J. Hum. Genet. 63:727-36
38. Tanaka K, Nakafuku M, Satoh T, Marshall MS, Gibbs JB, et al. 1990. S. cerevisiae genes IRA1 and IRA2 encode proteins that may be functionally equivalent to mammalian ras GTPase activating protein. Cell 60:803-7
39. The I, Hannigan GE, Cowley GS, Reginald S, Zhong Y, et al. 1997. Rescue of a Drosophila NF1 mutant phenotype by protein kinase A. Science 276:791-94
40. C. elegans Sequencing Consortium. 1998. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282:2012-18
41. Bretscher A, Edwards K, Fehon RG. 2002. ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 3:586-99
42. Golovnina K, Blinov A, Akhmametyeva EM, Omelyanchuk LV, Chang LS. 2005. Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2) tumorsuppressor gene. BMC Evol. Biol. 5:69
43. LaJeunesse DR, McCartney BM, Fehon RG. 1998. Structural analysis of Drosophila merlin reveals functional domains important for growth control and subcellular localization. J. Cell Biol. 141:1589-99
44. McCartney BM, Kulikauskas RM, LaJeunesse DR, Fehon RG. 2000. The neurofibromatosis-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation. Development 127:1315-24
45. Gobel V, Barrett PL, Hall DH, Fleming JT. 2004. Lumen morphogenesis in C. elegans requires the membrane-cytoskeleton linker erm-1. Dev. Cell 6:865-73
46. Bernards A, Snijders AJ, Hannigan GE, Murthy AE, Gusella JF. 1993. Mouse neurofibromatosis type 1 cDNA sequence reveals high degree of conservation of both coding and noncoding mRNA segments. Hum. Mol. Genet. 2:645-50
47. Haase VH, Trofatter JA, MacCollin M, Tarttelin E, Gusella JF, Ramesh V. 1994. The murine NF2 homologue encodes a highly conserved merlin protein with alternative forms. Hum. Mol. Genet. 3:407-11
48. Brannan CI, Perkins AS, Vogel KS, Ratner N, Nordlund ML, et al. 1994. Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes Dev. 8:1019-29
49. Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A, Weinberg RA. 1994. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat. Genet. 7:353-61
50. McClatchey AI, Saotome I, Ramesh V, Gusella JF, Jacks T. 1997. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. Genes Dev. 11:1253-65
51. McClatchey AI, Saotome I, Mercer K, Crowley D, Gusella JF, et al. 1998. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev. 12:1121-33
52. Giovannini M, Robanus-Maandag E, van der Valk M, Niwa-Kawakita M, Abramowski V, et al. 2000. Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev. 14:1617-30
53. Zhu Y, Romero MI, Ghosh P, Ye Z, Charnay P, et al. 2001. Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev. 15:859-76
54. Gitler AD, Zhu Y, Ismat FA, Lu MM, Yamauchi Y, et al. 2003. Nf1 has an essential role in endothelial cells. Nat. Genet. 33:75-79
55. Alonso ME, Bello MJ, Gonzalez-Gomez P, Arjona D, de Campos JM, et al. 2004. Aberrant CpG island methylation of multiple genes in ependymal tumors. J. Neurooncol. 67:159-65
56. Kimura Y, Koga H, Araki N, Mugita N, Fujita N, et al. 1998. The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas. Nat. Med. 4:915-22
57. Shaw RJ, Paez JG, Curto M, Yaktine A, Pruitt WM, et al. 2001. The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling. Dev. Cell 1:63-72
58. Cichowski K, Shih TS, Schmitt E, Santiago S, Reilly K, et al. 1999. Mouse models of tumor development in neurofibromatosis type 1. Science 286:2172-76
59. Vogel KS, Klesse LJ, Velasco-Miguel S, Meyers K, Rushing EJ, Parada LF. 1999. Mouse tumor model for neurofibromatosis type 1. Science 286:2176-79
60. Reilly KM, Loisel DA, Bronson RT, McLaughlin ME, Jacks T. 2000. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat. Genet. 26:109-13
61. Reilly KM, Broman KW, Bronson RT, Tsang S, Loisel DA, et al. 2006. An imprinted locus epistatically influences Nstr1 and Nstr2 to control resistance to nerve sheath tumors in a neurofibromatosis type 1 mouse model. Canc. Res. 66:62-68
62. Reilly KM, Tuskan RG, Christy E, Loisel DA, Ledger J, et al. 2004. Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. Proc. Natl. Acad. Sci. USA 101:13008-13
63. Stemmer-Rachamimov AO, Louis DN, Nielsen GP, Antonescu CR, Borowsky AD, et al. 2004. Comparative pathology of nerve sheath tumors in mouse models and humans. Canc. Res. 64:3718-24
64. Robanus-Maandag E, Giovannini M, van der Valk M, Niwa-Kawakita M, Abramowski V, et al. 2004. Synergy of Nf2 and p53 mutations in development of malignant tumours of neural crest origin. Oncogene 23:6541-47
65. Zhu Y, Guignard F, Zhao D, Liu L, Burns DK, et al. 2005. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Canc. Cell 8:119-30
66. Eden A, Gaudet F, Waghmare A, Jaenisch R. 2003. Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300:455
67. Bernards A, Settleman J. 2004. GAP control: regulating the regulators of small GTPases. Trends Cell Biol. 14:377-85
68. Cichowski K, Jacks T. 2001. NF1 tumor suppressor gene function: narrowing the GAP. Cell 104:593-604
69. Guo HF, The I, Hannan F, Bernards A, Zhong Y. 1997. Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides. Science 276:795-98
70. Guo HF, Tong J, Hannan F, Luo L, Zhong Y. 2000. A neurofibromatosis-1- regulated pathway is required for learning in Drosophila. Nature 403:895-98
71. Williams JA, Su HS, Bernards A, Field J, Sehgal A. 2001. A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/MAPK. Science 293:2251-56
72. Dasgupta B, Dugan LL, Gutmann DH. 2003. The neurofibromatosis 1 gene product neurofibromin regulates pituitary adenylate cyclase-activating polypeptide-mediated signaling in astrocytes. J. Neurosci. 23:8949-54
73. Kim HA, Ratner N, Roberts TM, Stiles CD. 2001. Schwann cell proliferative responses to cAMP and Nf1 are mediated by cyclin D1. J. Neurosci. 21:1110-16
74. Tong J, Hannan F, Zhu Y, Bernards A, Zhong Y. 2002. Neurofibromin regulates G protein-stimulated adenylyl cyclase activity. Nat. Neurosci. 5:95-96
75. Kim HA, DeClue JE, Ratner N. 1997. cAMP-dependent protein kinase A is required for Schwann cell growth: interactions between the cAMP and neuregulin/tyrosine kinase pathways. J. Neurosci. Res. 49:236-47
76. Hannan F, Ho I, Tong JJ, Zhu Y, Nurnberg P, Zhong Y. 2006. Effect of neurofibromatosis type 1 mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras. Hum. Mol. Genet. 15:1087-98
77. Philips MR. 2005. Compartmentalized signaling of Ras. Biochem. Soc. Trans. 33:657-61
78. Johannessen CM, Reczek EF, James MF, Brems H, Legius E, Cichowski K. 2005. The NF1 tumor suppressor critically regulates TSC2 and mTOR. Proc. Natl. Acad. Sci. USA 102:8573-78
79. Dasgupta B, Yi Y, Chen DY, Weber JD, Gutmann DH. 2005. Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors. Canc. Res. 65:2755-60
80. Cichowski K, Santiago S, Jardim M, Johnson BW, Jacks T. 2003. Dynamic regulation of the Ras pathway via proteolysis of the NF1 tumor suppressor. Genes Dev. 17:449-54
81. Ciechanover A, Orian A, Schwartz AL. 2000. Ubiquitin-mediated proteolysis: biological regulation via destruction. Bioessays 22:442-51
82. McClatchey AI, Giovannini M. 2005. Membrane organization and tumorigenesis - the NF2 tumor suppressor, Merlin. Genes Dev. 19:2265-77
83. Gonzalez-Agosti C, Xu L, Pinney D, Beauchamp R, Hobbs W, et al. 1996. The merlin tumor suppressor localizes preferentially in membrane ruffles. Oncogene 13:1239-47
84. Maeda M, Matsui T, Imamura M, Tsukita S, Tsukita S. 1999. Expression level, subcellular distribution and rho-GDI binding affinity of merlin in comparison with Ezrin/Radixin/Moesin proteins. Oncogene 18:4788-97
85. Lallemand D, Curto M, Saotome I, Giovannini M, McClatchey AI. 2003. NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes Dev. 17:1090-100
86. Lutchman M, Rouleau GA. 1995. The neurofibromatosis type 2 gene product, schwannomin, suppresses growth of NIH 3T3 cells. Canc. Res. 55:2270-74
87. Tikoo A, Varga M, Ramesh V, Gusella J, Maruta H. 1994. An anti-Ras function of neurofibromatosis type 2 gene product (NF2/Merlin). J. Biol. Chem. 269:23387-90
88. Gronholm M, Sainio M, Zhao F, Heiska L, Vaheri A, Carpen O. 1999. Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin. J. Cell Sci. 112(Pt. 6):895-904
89. Nguyen R, Reczek D, Bretscher A. 2001. Hierarchy of merlin and ezrin N- and C-terminal domain interactions in homo- and heterotypic associations and their relationship to binding of scaffolding proteins EBP50 and E3KARP. J. Biol. Chem. 276:7621-29
90. Sherman L, Xu HM, Geist RT, Saporito-Irwin S, Howells N, et al. 1997. Interdomain binding mediates tumor growth suppression by the NF2 gene product. Oncogene 15:2505-9
91. Pearson MA, Reczek D, Bretscher A, Karplus PA. 2000. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101:259-70
92. Shimizu T, Seto A, Maita N, Hamada K, Tsukita S, et al. 2002. Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain. J. Biol. Chem. 277:10332-36
93. McClatchey AI. 2003. Merlin and ERM proteins: unappreciated roles in cancer development? Nat. Rev. Canc. 3:877-83
94. Speck O, Hughes SC, Noren NK, Kulikauskas RM, Fehon RG. 2003. Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity. Nature 421:83-87
95. Kissil JL, Johnson KC, Eckman MS, Jacks T. 2002. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. J. Biol. Chem. 277:10394-99
96. Kissil JL, Wilker EW, Johnson KC, Eckman MS, Yaffe MB, Jacks T. 2003. Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol. Cell 12:841-49
97. Xiao GH, Beeser A, Chernoff J, Testa JR. 2002. p21-activated kinase links Rac/Cdc42 signaling to merlin. J. Biol. Chem. 277:883-86
98. Morrison H, Sherman LS, Legg J, Banine F, Isacke C, et al. 2001. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 15:968-80
99. Kolch W. 2003. Erbin: sorting out ErbB2 receptors or giving Ras a break? Sci. STKE 199:pe37
100. + exchanger regulatory factor stabilizes epidermal growth factor receptors at the cell surface. Mol. Biol. Cell 15:5470-80
101. + exchange, is a common interactor for merlin and ERM (MERM) proteins. J. Biol. Chem. 273:1273-76
102. Rangwala R, Banine F, Borg JP, Sherman LS. 2005. Erbin regulates mitogen-activated protein (MAP) kinase activation and MAP kinase-dependent interactions between Merlin and adherens junction protein complexes in Schwann cells. J. Biol. Chem. 280:11790-97
103. Wiederhold T, Lee MF, James M, Neujahr R, Smith N, et al. 2004. Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2. Oncogene 23:8815-25
104. McCartney BM, Fehon RG. 1996. Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin. J. Cell Biol. 133:843-52
105. Stickney JT, Bacon WC, Rojas M, Ratner N, Ip W. 2004. Activation of the tumor suppressor merlin modulates its interaction with lipid rafts. Canc. Res. 64:2717-24
106. Maitra S, Kulikauskas RM, Gavilan H, Fehon RG. 2006. The tumor suppressors Merlin and expanded function cooperatively to modulate receptor endocytosis and signaling. Curr. Biol. 16:702-9
107. Kluwe L, Friedrich R, Mautner VF. 1999. Loss of NF1 allele in Schwann cells but not in fibroblasts derived from an NF1-associated neurofibroma. Genes Chromosomes Canc. 24:283-85
108. Serra E, Rosenbaum T, Winner U, Aledo R, Ars E, et al. 2000. Schwann cells harbor the somatic NF1 mutation in neurofibromas: evidence of two different Schwann cell subpopulations. Hum. Mol. Genet. 9:3055-64
109. Voiculescu O, Charnay P, Schneider-Maunoury S. 2000. Expression pattern of a Krox20/Cre knock-in allele in the developing hindbrain, bones, and peripheral nervous system. Genesis 26:123-26
110. Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi AB, et al. 1994. Krox-20 controls myelination in the peripheral nervous system. Nature 371:796-99
111. Ingram DA, Yang FC, Travers JB, Wenning MJ, Hiatt K, et al. 2000. Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo. J. Exp. Med. 191:181-88
112. Santarosa M, Ashworth A. 2004. Haploinsufficiency for tumor suppressor genes: when you don't need to go all the way. Biochim. Biophys. Acta 1654:105-22
113. Greenblatt MS, Bennett WP, Hollstein M, Harris CC. 1994. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Canc. Res. 54:4855-78
114. Menon AG, Anderson KM, Riccardi VM, Chung RY, Whaley JM, et al. 1990. Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. Proc. Natl. Acad. Sci. USA 87:5435-39
115. Berner JM, Sorlie T, Mertens F, Henriksen J, Saeter G, et al. 1999. Chromosome band 9p21 is frequently altered in malignant peripheral nerve sheath tumors: studies of CDKN2A and other genes of the pRB pathway. Genes Chromosomes Canc. 26:151-60
116. Kourea HP, Orlow I, Scheithauer BW, Cordon-Cardo C, Woodruff JM. 1999. Deletions of the INK4A gene occur in malignant peripheral nerve sheath tumors but not in neurofibromas. Am. J. Pathol. 155:1855-60
117. Nielsen GP, Stemmer-Rachamimov AO, Ino Y, Moller MB, Rosenberg AE, Louis DN. 1999. Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation. Am. J. Pathol. 155:1879-84
118. Sherr CJ. 2004. Principles of tumor suppression. Cell 116:235-46
119. DeClue JE, Heffelfinger S, Benvenuto G, Ling B, Li S, et al. 2000. Epidermal growth factor receptor expression in neurofibromatosis type 1-related tumors and NF1 animal models. J. Clin. Invest. 105:1233-41
120. Holland EC. 2001. Gliomagenesis: genetic alterations and mouse models. Nat. Rev. Genet. 2:120-29
121. Bajenaru ML, Zhu Y, Hedrick NM, Donahoe J, Parada LF, Gutmann DH. 2002. Astrocyte-specific inactivation of the neurofibromatosis 1 gene (NF1) is insufficient for astrocytoma formation. Mol. Cell Biol. 22:5100-13
122. Zhu Y, Harada T, Liu L, Lush ME, Guignard F, et al. 2005. Inactivation of NF1 in CNS causes increased glial progenitor proliferation and optic glioma formation. Development 132:5577-88
123. Lauchle JO, Braun BS, Loh ML, Shannon K. 2006. Inherited predispositions and hyperactive Ras in myeloid leukemogenesis. Pediatr. Blood Canc. 46:579-85
124. Miles DK, Freedman MH, Stephens K, Pallavicini M, Sievers EL, et al. 1996. Patterns of hematopoietic lineage involvement in children with neurofibromatosis type 1 and malignant myeloid disorders. Blood 88:4314-20
125. Shannon KM, O'Connell P, Martin GA, Paderanga D, Olson K, et al. 1994. Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. N. Engl. J. Med. 330:597-601
126. Bollag G, Clapp DW, Shih S, Adler F, Zhang YY, et al. 1996. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in hematopoietic cells. Nat. Genet. 12:144-48
127. Kalra R, Paderanga DC, Olson K, Shannon KM. 1994. Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras. Blood 84:3435-39
128. Miyauchi J, Asada M, Sasaki M, Tsunematsu Y, Kojima S, Mizutam S. 1994. Mutations of the N-ras gene in juvenile chronic myelogenous leukemia. Blood 83:2248-54
129. Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, et al. 2001. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat. Genet. 29:465-68
130. Neel BG, Gu H, Pao L. 2003. The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem. Sci. 28:284-93
131. Largaespada DA, Brannan CI, Jenkins NA, Copeland NG. 1996. Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nat. Genet. 12:137-43
132. Zhang YY, Vik TA, Ryder JW, Srour EF, Jacks T, et al. 1998. Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response to multiple cytokines. J. Exp. Med. 187:1893-902
133. Birnbaum RA, O'Marcaigh A, Wardak Z, Zhang YY, Dranoff G, et al. 2000. Nf1 and Gmcsf interact in myeloid leukemogenesis. Mol. Cell 5:189-95
134. Mahgoub N, Taylor BR, Gratiot M, Kohl NE, Gibbs JB, et al. 1999. In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells. Blood 94:2469-76
135. Le DT, Kong N, Zhu Y, Lauchle JO, Aiyigari A, et al. 2004. Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood 103:4243-50
136. Silva AJ, Frankland PW, Marowitz Z, Friedman E, Laszlo GS, et al. 1997. A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Nat. Genet. 15:281-84
137. Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, et al. 2002. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415:526-30
138. Li W, Cui Y, Kushner SA, Brown RA, Jentsch JD, et al. 2005. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr. Biol. 15:1961-67
139. Woods R, Friedman JM, Evans DG, Baser ME, Joe H. 2003. Exploring the "two-hit hypothesis" in NF2: tests of two-hit and three-hit models of vestibular schwannoma development. Genet. Epidemiol. 24:265-72
140. Garratt AN, Britsch S, Birchmeier C. 2000. Neuregulin, a factor with many functions in the life of a schwann cell. Bioessays 22:987-96
141. Nakai Y, Zheng Y, MacCollin M, Ratner N. 2006. Temporal control of Rac in Schwann cell-axon interaction is disrupted in NF2-mutant schwannoma cells. J. Neurosci. 26:3390-95
142. Pelton PD, Sherman LS, Rizvi TA, Marchionni MA, Wood P, et al. 1998. Ruffling membrane, stress fiber, cell spreading and proliferation abnormalities in human Schwannoma cells. Oncogene 17:2195-209
143. Lusis E, Gutmann DH. 2004. Meningioma: an update. Curr. Opin. Neurol. 17:687-92
144. Kalamarides M, Niwa-Kawakita M, Leblois H, Abramowski V, Perricaudet M, et al. 2002. Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse. Genes Dev. 16:1060-65
145. Lechner JF, Tesfaigzi J, Gerwin BI. 1997. Oncogenes and tumor-suppressor genes in mesothelioma - a synopsis. Environ, Health Perspect. 105(Suppl. 5):1061-67
146. Baser ME, Rai H, Wallace AJ, Evans DG. 2005. Neurofibromatosis 2 (NF2) and malignant mesothelioma in a man with a constitutional NF2 missense mutation. Fam. Canc. 4:321-22
147. Altomare DA, Vaslet CA, Skele KL, De Rienzo A, Devarajan K, et al. 2005. A mouse model recapitulating molecular features of human mesothelioma. Canc. Res. 65:8090-95
148. Fleury-Feith J, Lecomte C, Renier A, Matrat M, Kheuang L, et al. 2003. Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours. Oncogene 22:3799-805