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:: Volume 29, Issue 2 (Summer 2019) ::
MEDICAL SCIENCES 2019, 29(2): 101-116 Back to browse issues page
The molecular genetics of neurofibromatosis type 1 and its future prospective
Mohammad Reza Nooridaloii 1, Elham Boustanipour2
1- , Department of Medical Genetics, Faculty of Medicine Tehran of Medical Sciences, Tehran, Iran , nooridaloii@sina.tums.ac.ir
2- MSc Student, Department of Medical Genetics, Faculty of Medicine Tehran of Medical Sciences, Tehran, Iran
Abstract:   (1031 Views)
Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that is caused through loss of function mutations of a tumor suppressor gene termed neurofibromin 1. Therapeutic decisions are presently restricted for NF1-associated tumors, where treatment is often restricted to thorough surgical resection with perfect margins. In this review article, the multifunctional role of neurofibromin in tumor suppression has been discussed. While neurofibromin inhibits proliferative growth through blockade RAS-mediated signal transduction, neurofibromin should also be considered as a modulator of cell motility and cell adhesion. Through interfacing with the cytoskeleton and membrane structures, neurofibromin acts as a negative regulator of RHO/ROCK signaling pathways involved in cytoskeletal dynamics that are involved in proper neuronal expansion.
The loss of function of neurofibromin through genetic mutation results in heightened cell proliferation and migration, predisposing NF1 patients to cancer. Malignant peripheral nerve sheath tumors (MPNSTs) can be developed from benign neurofibromas and are the main cause of death amongst NF1 patients. Recent researchers in MPNSTs have been attempting to reveal key molecular events that lead MPNSTs to malignancy. Advances regarding malignant drivers involved in cell migration, cell invasion and angiogenic signaling are discussed in this review, where these findings will likely influence future therapies for both NF1 and related sporadic cancers.
Keywords: Neurofibromatosis type 1, Plexiform Neurofibromatosis, MPNST.
Keywords: Neurofibromatosis type 1, Plexiform Neurofibromatosis, MPNST.
Full-Text [PDF 1000 kb]   (529 Downloads)    
Semi-pilot: Review | Subject: Genetic
Received: 2018/11/26 | Accepted: 2019/01/13 | Published: 2019/06/16
1. Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: First descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes. Am J Med Genet Part A 2018;176:515-50. [DOI:10.1002/ajmg.a.38486] [PMID]
2. Noori-Daloii MR, Kavoosi S, Rahimi Rad N. CRISPR/Cas9: high throughput genome editing molecular tool. Med Sci J Islamic Azad Univ 2017;27:223-36. [In Persian]
3. Kuiper M. Neurological and appearance-related symptoms in children with neurofibromatosis type 1 (NF1): The relationship between NF1 severity and cognitive and behavioural outcomes [MSc Thesis]. Leiden: Leiden University; 2011.
4. Noori-Daloii M. Medical molecular genetics in the third millennium. Tehran: Samer and Nashre Akhar Publishing, 2009. [In Persian]
5. Costa DdS, de Paula JJ, Alvim-Soares Jr AM, Pereira PA, Malloy-Diniz LF, Rodrigues LO, et al. COMT Val158Met Polymorphism Is Associated with Verbal Working Memory in Neurofibromatosis Type 1. Front Hum Neurosci 2016;10:334. [DOI:10.3389/fnhum.2016.00334] [PMID] [PMCID]
6. Burris CK, Stier MA, Salamat S, Thomas S, Lauderdale S, Raven ML, et al. Neurofibromatosis type 1: a neuro-psycho-cutaneous syndrome? Orbit 2018;37:208-11. [DOI:10.1080/01676830.2017.1383476] [PMID]
7. Dogra BB, Rana KS. Facial plexiform neurofibromatosis: a surgical challenge. Dermatol Online J 2013;4:195. [DOI:10.4103/2229-5178.115515] [PMID] [PMCID]
8. Barker D, Wright E, Nguyen K, Cannon L, Fain P, Goldgar D, et al. Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science 1987;236:1100-2. [DOI:10.1126/science.3107130] [PMID]
9. Seizinger B, Rouleau G, Ozelius L, Lane A, Faryniarz A, Chao M, et al. Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene. Cell 1987;49:589-94. [DOI:10.1016/0092-8674(87)90534-4]
10. Wallace MR, Marchuk DA, Andersen LB, Letcher R, Odeh HM, Saulino AM, et al. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 1990;249:181-6. [DOI:10.1126/science.2134734] [PMID]
11. Fain P, Goldgar D, Wallace M, Collins F, Wright E, Nguyen K, et al. Refined physical and genetic mapping of the NF1 region on chromosome 17. Am J Hum Genet 1989;45:721.
12. Collins FS, O'Connell P, Ponder BA, Seizinger BR. Progress towards identifying the neurofibromatosis (NF1) gene. Trends Genet 1989;5:217-21. [DOI:10.1016/0168-9525(89)90085-1]
13. Menon AG, Ledbetter DH, Rich DC, Seizinger BR, Rouleau GA, Michels VF, et al. Characterization of a translocation within the von Recklinghausen neurofibromatosis region of chromosome 17. Genomics 1989;5:245-9. [DOI:10.1016/0888-7543(89)90053-0]
14. Viskochil D, Buchberg AM, Xu G, Cawthon RM, Stevens J, Wolff RK, et al. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 1990;62:187-92. [DOI:10.1016/0092-8674(90)90252-A]
15. Ratner N, Miller SJ. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer 2015;15:290. [DOI:10.1038/nrc3911] [PMID] [PMCID]
16. Seminog OO, Goldacre MJ. Risk of benign tumours of nervous system, and of malignant neoplasms, in people with neurofibromatosis: population-based record-linkage study. Br J Cancer 2013;108:193. [DOI:10.1038/bjc.2012.535] [PMID] [PMCID]
17. Barron VA, Lou H. Alternative splicing of the neurofibromatosis type I pre-mRNA. Biosci Rep 2012;32:131-8. [DOI:10.1042/BSR20110060] [PMID] [PMCID]
18. Mitin N, Rossman KL, Der CJ. Signaling interplay in Ras superfamily function. Curr Biol 2005;15:R563-74. [DOI:10.1016/j.cub.2005.07.010] [PMID]
19. McTaggart S. Isoprenylated proteins. Cell Mol Life Sci 2006;63:255-67. [DOI:10.1007/s00018-005-5298-6] [PMID]
20. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003;3:11. [DOI:10.1038/nrc969] [PMID]
21. Goodsell DS. The molecular perspective: the ras oncogene. Oncologist 1999;4:263-4.
22. Hiatt KK, Ingram DA, Zhang Y, Bollag G, Clapp DW. Neurofibromin GTPase-activating protein-related domains restore normal growth in Nf1−/− cells. J Biol Chem 2001;276:7240-5. [DOI:10.1074/jbc.M009202200] [PMID]
23. Lavoie H, Therrien M. Regulation of RAF protein kinases in ERK signalling. Nat Rev Mol Cell Biol 2015;16:281. [DOI:10.1038/nrm3979] [PMID]
24. Aramini JM, Vorobiev SM, Tuberty LM, Janjua H, Campbell ET, Seetharaman J, et al. The RAS-binding domain of human BRAF protein serine/threonine kinase exhibits allosteric conformational changes upon binding HRAS. Structure 2015;23:1382-93. [DOI:10.1016/j.str.2015.06.003] [PMID] [PMCID]
25. Hancock JF, Robert G. Ras plasma membrane signalling platforms. Biochem J 2005;389:1-11. [DOI:10.1042/BJ20050231] [PMID] [PMCID]
26. Welti S, Kühn S, D'angelo I, Brügger B, Kaufmann D, Scheffzek K. Structural and biochemical consequences of NF1 associated nontruncating mutations in the Sec14‐PH module of neurofibromin. Hum Mutat 2011;32:191-7. [DOI:10.1002/humu.21405] [PMID]
27. Mavrakis KJ, Zhu H, Silva RL, Mills JR, Teruya-Feldstein J, Lowe SW, et al. Tumorigenic activity and therapeutic inhibition of Rheb GTPase. Genes Dev 2008;22:2178-88. [DOI:10.1101/gad.1690808] [PMID] [PMCID]
28. Atala A. Re: mTORC1 Drives HIF-1α and VEGF-A Signalling via Multiple Mechanisms Involving 4E-BP1, S6K1 and STAT3. J Urol 2016;195:524-5. [DOI:10.1016/j.juro.2015.10.121]
29. Ozawa T, Araki N, Yunoue S, Tokuo H, Feng L, Patrakitkomjorn S, et al. The neurofibromatosis type 1 gene product neurofibromin enhances cell motility by regulating actin filament dynamics via the Rho-ROCK-LIMK2-cofilin pathway. J Biol Chem 2005;280:39524-33. [DOI:10.1074/jbc.M503707200] [PMID]
30. Gregory PE, Gutmann DH, Mitchell A, Park S, Boguski M, Jacks T, et al. Neurofibromatosis type 1 gene product (neurofibromin) associates with microtubules. Somatic cell Mol Genet 1993;19:265-74. [DOI:10.1007/BF01233074]
31. Kweh F, Zheng M, Kurenova E, Wallace M, Golubovskaya V, Cance WG. Neurofibromin physically interacts with the N‐terminal domain of focal adhesion kinase. Mol Carcinog 2009;48:1005-17. [DOI:10.1002/mc.20552] [PMID] [PMCID]
32. Tsai PI, Wang M, Kao HH, Cheng YJ, Walker JA, Chen RH, et al. Neurofibromin mediates FAK signaling in confining synapse growth at Drosophila neuromuscular junctions. J Neurosci 2012;32:16971-81. [DOI:10.1523/JNEUROSCI.1756-12.2012] [PMID]
33. Feng L, Yunoue S, Tokuo H, Ozawa T, Zhang D, Patrakitkomjorn S, et al. PKA phosphorylation and 14‐3‐3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin. FEBS Lett 2004;557:275-82. [DOI:10.1016/S0014-5793(03)01507-2]
34. Sadjadi A, Nouraie M, Mohagheghi MA, Mousavi-Jarrahi A, Malekezadeh R, Parkin DM. Cancer occurrence in Iran in 2002, an international perspective. Asian Pac J Cancer Prev 2005;6:359.
35. Korf BR. Malignancy in neurofibromatosis type 1. Oncologist 2000;5:477-85. [DOI:10.1634/theoncologist.5-6-477] [PMID]
36. Zehou O, Fabre E, Zelek L, Sbidian E, Ortonne N, Banu E, et al. Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: a 10-year institutional review. Orphanet J Rare Dis 2013;8:127. [DOI:10.1186/1750-1172-8-127] [PMID] [PMCID]
37. Kahn J, Gillespie A, Tsokos M, Ondos J, Dombi E, Camphausen K, et al. Radiation therapy in management of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Front Oncol 2014;4:324. [DOI:10.3389/fonc.2014.00324] [PMID] [PMCID]
38. Yang JC, Chang AE, Baker AR, Sindelar WF, Danforth DN, Topalian SL, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998;16:197-203. [DOI:10.1200/JCO.1998.16.1.197] [PMID]
39. Du X, Yang J, Ylipää A, Zhu Z. Genomic amplification and high expression of EGFR are key targetable oncogenic events in malignant peripheral nerve sheath tumor. J Hematol Oncol 2013;6:93. [DOI:10.1186/1756-8722-6-93] [PMID] [PMCID]
40. Beert E, Brems H, Daniëls B, De Wever I, Van Calenbergh F, Schoenaers J, et al. Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosomes Cancer 2011;50:1021-32. [DOI:10.1002/gcc.20921] [PMID]
41. Noori-Daloii M, Zekri A. Aura kinase family roles in cancer diagnosis and treatment: a review article. Med Sci J Islamic Azad Univ 2011;21:71-81. [In Persian]
42. Upadhyaya M, Spurlock G, Thomas L, Thomas NS, Richards M, Mautner VF, et al. Microarray‐based copy number analysis of neurofibromatosis type‐1 (NF1)‐associated malignant peripheral nerve sheath tumors reveals a role for Rho-GTPase pathway genes in NF1 tumorigenesis. Hum Mutat 2012;33:763-76. [DOI:10.1002/humu.22044] [PMID]
43. Tabone-Eglinger S, Bahleda R, Côté JF, Terrier P, Vidaud D, Cayre A, et al. Frequent EGFR positivity and overexpression in high-grade areas of human MPNSTs. Sarcoma 2008;2008. [DOI:10.1155/2008/849156] [PMID] [PMCID]
44. Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, et al. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol 2013;31:412. [DOI:10.1200/JCO.2012.45.0494] [PMID] [PMCID]
45. Ohishi J, Aoki M, Nabeshima K, Suzumiya J, Takeuchi T, Ogose A, et al. Imatinib mesylate inhibits cell growth of malignant peripheral nerve sheath tumors in vitro and in vivo through suppression of PDGFR-β. BMC Cancer 2013;13:224. [DOI:10.1186/1471-2407-13-224] [PMID] [PMCID]
46. Gudena V, Verma N, Post G, Kizziah M, Fenning R, Montero AJ. Metastatic chest wall malignant schwannoma responding to sorafenib: case report and literature review. Cancer Biol Ther 2008;7:810-3. [DOI:10.4161/cbt.7.6.5932] [PMID]
47. Ambrosini G, Cheema HS, Seelman S, Teed A, Sambol EB, Singer S, et al. Sorafenib inhibits growth and mitogen-activated protein kinase signaling in malignant peripheral nerve sheath cells. Mol Cancer Ther 2008;7:890-6. [DOI:10.1158/1535-7163.MCT-07-0518] [PMID] [PMCID]
48. Thomas LE, Winston J, Rad E, Mort M, Dodd KM, Tee AR, et al. Evaluation of copy number variation and gene expression in neurofibromatosis type-1-associated malignant peripheral nerve sheath tumours. Hum Genom 2015;9:3. [DOI:10.1186/s40246-015-0025-3] [PMID] [PMCID]
49. Teixeira F, Martinez-Palomo A, Riccardi V, Fernandez-Diez J. Vascular changes in cutaneous neurofibromas. Neurofibromatosis 1988;1:5-16.
50. Gesundheit B, Parkin P, Greenberg M, Baruchel S, Senger C, Kapelushnik J, et al. The role of angiogenesis in the transformation of plexiform neurofibroma into malignant peripheral nerve sheath tumors in children with neurofibromatosis type 1. J Pediatr Hematol Oncol 2010;32:548-53. [DOI:10.1097/MPH.0b013e3181e887c7] [PMID]
51. Rad E, Dodd K, Thomas L, Upadhyaya M, Tee A. STAT3 and HIF1α signaling drives oncogenic cellular phenotypes in malignant peripheral nerve sheath tumors. Mol Cancer Res 2015;13:1149-60. [DOI:10.1158/1541-7786.MCR-14-0182] [PMID]
52. Rahrmann EP, Watson AL, Keng VW, Choi K, Moriarity BS, Beckmann DA, et al. Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis. Nature Genet 2013;45:756. [DOI:10.1038/ng.2641] [PMID] [PMCID]
53. Watson AL, Rahrmann EP, Moriarity BS, Choi K, Conboy CB, Greeley AD, et al. Canonical Wnt/β-catenin signaling drives human Schwann cell transformation, progression, and tumor maintenance. Cancer Discov 2013;3:674-89. [DOI:10.1158/2159-8290.CD-13-0081] [PMID] [PMCID]
54. Luscan A, Masliah-Planchon J, Laurendeau I, Ortonne N, Varin J, Lallemand F, et al. The activation of the WNT signalling pathway is a hallmark in Neurofibromatosis type 1 tumorigenesis. Clin Cancer Res 2013;20:358-71. [DOI:10.1158/1078-0432.CCR-13-0780] [PMID]
55. Curtin JC, Lorenzi MV. Drug discovery approaches to target Wnt signaling in cancer stem cells. Oncotarget 2010;1:552. [DOI:10.18632/oncotarget.191] [PMID] [PMCID]
56. Bradtmöller M, Hartmann C, Zietsch J, Jäschke S, Mautner VF, Kurtz A, et al. Impaired Pten expression in human malignant peripheral nerve sheath tumours. PLoS One 2012;7:e47595. [DOI:10.1371/journal.pone.0047595] [PMID] [PMCID]
57. Reilly KM. Extending the convergence of canonical Wnt signaling and classic cancer pathways for treatment of malignant peripheral nerve sheath tumors. Cancer discov 2013;3:610-2. [DOI:10.1158/2159-8290.CD-13-0192] [PMID] [PMCID]
58. De Raedt T, Beert E, Pasmant E, Luscan A, Brems H, Ortonne N, et al. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 2014;514:247. [DOI:10.1038/nature13561] [PMID]
59. Kirmizis A, Bartley SM, Farnham PJ. Identification of the Polycomb Group Protein SU (Z) 12 as a Potential Molecular Target for Human Cancer Therapy1. Mol Cancer Ther 2003;2:113-21.
60. Li H, Cai Q, Wu H, Vathipadiekal V, Dobbin ZC, Li T, et al. SUZ12 promotes human epithelial ovarian cancer by suppressing apoptosis via silencing HRK. Mol Cancer Res 2012;10:1462-72. [DOI:10.1158/1541-7786.MCR-12-0335] [PMID] [PMCID]
61. Pasmant E, Masliah-Planchon J, Lévy P, Laurendeau I, Ortonne N, Parfait B, et al. Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients. Mol Med 2011;17:79. [DOI:10.2119/molmed.2010.00079] [PMID] [PMCID]
62. Liu C, Shi X, Wang L, Wu Y, Jin F, Bai C, et al. SUZ12 is involved in progression of non-small cell lung cancer by promoting cell proliferation and metastasis. Tumor Biol 2014;35:6073-82. [DOI:10.1007/s13277-014-1804-5] [PMID]
63. Noori-Daloii M, Alvandi E. Micro RNA: Small but full of mystery and use: a review article. Tehran Univ Med J 2006;64:5-18. [In Persian]
64. Noori-Daloii MR, Nejatizadeh A. MicroRNA in disease and health: diagnostic and therapeutic potentials. In: Kang C, Ed. Gene ttherapy- development and future perspectives. USA: InThec; 2011. P. 93-120
65. Völkel P, Dupret B, Le Bourhis X, Angrand PO. Diverse involvement of EZH2 in cancer epigenetics. Am J Transl Res 2015;7:175.
66. Masliah-Planchon J, Pasmant E, Luscan A, Laurendeau I, Ortonne N, Hivelin M, et al. MicroRNAome profiling in benign and malignant neurofibromatosis type 1-associated nerve sheath tumors: evidences of PTEN pathway alterations in early NF1 tumorigenesis. BMC Genomics 2013;14:473. [DOI:10.1186/1471-2164-14-473] [PMID] [PMCID]
67. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 2004;101:2999-3004. [DOI:10.1073/pnas.0307323101] [PMID] [PMCID]
68. Presneau N, Eskandarpour M, Shemais T, Henderson S, Halai D, Tirabosco R, et al. MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a tumour suppressor gene involved in tumour progression. Br J Cancer 2013;108:964. [DOI:10.1038/bjc.2012.518] [PMID] [PMCID]
69. Noori-Daloii MR, Vand Rajabpour F. Roles of miRNAs in gene expression regulation, apoptosis, diagnosis and treatment of cancer. Med Sci J Islamic Azad Univ 2011;21:151-61. [In Persian]
70. Walker JA, Upadhyaya M. Emerging therapeutic targets for neurofibromatosis type 1. Expert Opin Ther Targets 2018;22:419-37. [DOI:10.1080/14728222.2018.1465931] [PMID]
71. Liang XH, Sun H, Shen W, Wang S, Yao J, Migawa MT, et al. Antisense oligonucleotides targeting translation inhibitory elements in 5′ UTRs can selectively increase protein levels. Nucleic Acids Res 2017;45:9528-46. [DOI:10.1093/nar/gkx632] [PMID] [PMCID]
72. Gori JL, Hsu PD, Maeder ML, Shen S, Welstead GG, Bumcrot D. Delivery and specificity of CRISPR/Cas9 genome editing technologies for human gene therapy. Hum Gene Ther 2015;26:443-51. [DOI:10.1089/hum.2015.074] [PMID]
73. Hanemann CO, Blakeley JO, Nunes FP, Robertson K, Stemmer-Rachamimov A, Mautner V, et al. Current status and recommendations for biomarkers and biobanking in neurofibromatosis. Neurology 2016;87:S40-8. [DOI:10.1212/WNL.0000000000002932] [PMID] [PMCID]
74. Jones RE, Grimstead JW, Sedani A, Baird D, Upadhyaya M. Telomere erosion in NF1 tumorigenesis. Oncotarget 2017;8:40132. [DOI:10.18632/oncotarget.16981] [PMID] [PMCID]
75. De Raedt T, Walton Z, Yecies JL, Li D, Chen Y, Malone CF, et al. Exploiting cancer cell vulnerabilities to develop a combination therapy for ras-driven tumors. Cancer cell 2011;20:400-13. [DOI:10.1016/j.ccr.2011.08.014] [PMID] [PMCID]
76. Malone CF, Emerson C, Ingraham R, Barbosa W, Guerra S, Yoon H, et al. mTOR and HDAC inhibitors converge on the TXNIP/thioredoxin pathway to cause catastrophic oxidative stress and regression of RAS-driven tumors. Cancer Discov 2017;7:1450-63. [DOI:10.1158/2159-8290.CD-17-0177] [PMID] [PMCID]
77. Varin J, Poulain L, Hivelin M, Nusbaum P, Hubas A, Laurendeau I, et al. Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells. Oncotarget 2016;7:35753. [DOI:10.18632/oncotarget.7099] [PMID] [PMCID]
78. Patel AV, Eaves D, Jessen WJ, Rizvi TA, Ecsedy JA, Qian MG, et al. Ras-driven transcriptome analysis identifies aurora kinase A as a potential malignant peripheral nerve sheath tumor therapeutic target. Clin Cancer Res 2012;18:5020-30. [DOI:10.1158/1078-0432.CCR-12-1072] [PMID] [PMCID]
79. Varelas X. The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 2014;141(8):1614-26. [DOI:10.1242/dev.102376] [PMID]
80. Wu LMN, Deng Y, Wang J, Zhao C, Wang J, Rao R, et al. Programming of Schwann cells by Lats1/2-TAZ/YAP signaling drives malignant peripheral nerve sheath tumorigenesis. Cancer cell 2018;33:292-308. [DOI:10.1016/j.ccell.2018.01.005] [PMID] [PMCID]
81. Wegscheid ML, Anastasaki C, Gutmann DH. Human stem cell modeling in neurofibromatosis type 1 (NF1). Exp Neurol 2018;299:270-80. [DOI:10.1016/j.expneurol.2017.04.001] [PMID] [PMCID]
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Nooridaloii M R, Boustanipour E. The molecular genetics of neurofibromatosis type 1 and its future prospective . MEDICAL SCIENCES. 2019; 29 (2) :101-116
URL: http://tmuj.iautmu.ac.ir/article-1-1574-en.html

Volume 29, Issue 2 (Summer 2019) Back to browse issues page
فصلنامه علوم پزشکی دانشگاه آزاد اسلامی واحد پزشکی تهران Medical Science Journal of Islamic Azad Univesity - Tehran Medical Branch
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