The Neurofibromatosis type 1:A dominantly inherited tumors-predisposing disorder

• Authors: Maria Scalzone , Paola Coccia , Antonio Ruggiero , Ilaria Lazzareschi , Stefano Mastrangelo , Riccardo Riccardi
• Languages of publication: EN

Abstracts

EN

Neurofibromatosis type I (NF1) is a hereditary multisystem disease involving the skin and nervous system. It is the most common form of autosomal dominant phakomatoses with 100% penetrance but wide phenotypic variability. The NF1 gene is located on chromosome 17q11.2 and encodes for a tumour suppressor protein. Because affected individuals have an increased risk of tumor formation, this disorder is classified as inherited cancer syndrome. The risk of malignancies in NF1 affected patients is estimated to be 5–15% higher than in the general population. We reviewed clinical aspects and genetic mechanisms of tumorigenesis in NF1 affected patients.

Keywords

EN

Neurofibromatosis type I; Tumor; Pathogenesis; Children

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2009
• Volume: 4
• Issue: 1
• Pages: 11-16

Dates

published

1 - 3 - 2009

online

11 - 2 - 2009

Contributors

author

Maria Scalzone

• Department of Pediatrics, Division of Pediatric Oncology, Catholic University, “A. Gemelli” Hospital, 00168, Roma, Italy

author

Paola Coccia

• Department of Pediatrics, Division of Pediatric Oncology, Catholic University, “A. Gemelli” Hospital, 00168, Roma, Italy

author

Antonio Ruggiero

• Department of Pediatrics, Division of Pediatric Oncology, Catholic University, “A. Gemelli” Hospital, 00168, Roma, Italy

author

Ilaria Lazzareschi

• Department of Pediatrics, Division of Pediatric Oncology, Catholic University, “A. Gemelli” Hospital, 00168, Roma, Italy

author

Stefano Mastrangelo

• Department of Pediatrics, Division of Pediatric Oncology, Catholic University, “A. Gemelli” Hospital, 00168, Roma, Italy

author

Riccardo Riccardi

• Department of Pediatrics, Division of Pediatric Oncology, Catholic University, “A. Gemelli” Hospital, 00168, Roma, Italy

References

• [1] Friedman J.M., Riccardi V.M., Neurofibromatosis: phenotype, natural history and pathogenesis, 3rd ed., Baltimore, Johns Hopkins University Press, 1999
• [2] Riccardi V.M., Lewis R.A., Penetrance of von Recklinghausen neurofibromatosis: a distinction between predecessors and descendant, Am. J. Hum. Genet., 1988, 42, 284–289
• [3] Szudek J., Joe K., Friendman J.M., Analysis of Intrafamilial Phenotype Variation in Neurofibromatosis 1 (NF1), Genet. Epidem., 2002, 23, 150–164 http://dx.doi.org/10.1002/gepi.1129[Crossref]
• [4] Wallace M.R., Marchuk D.A., Andersen L.B., Letcher R., Odeh H.M., Saulino A.M., et al., Type 1 neurofibromatosis gene: identification of a larger transcript disrupted in three NG1 patients, Science, 1990, 249, 181–186 http://dx.doi.org/10.1126/science.2134734[Crossref]
• [5] Xu G.F., O’Connell P., Viskochil D., Cawthon R., Robertson M., Culver M., et al., The neurofibromatosis type 1 gene encodes a protein related to GAP, Cell, 1990, 62, 599–608 http://dx.doi.org/10.1016/0092-8674(90)90024-9[Crossref]
• [6] Walzer L., Thompson D., Ponder B.M., Frayling I., Baralle D., A prospective study of neurofibromatosis type I cancer incidence in the UK, Brit. J. Cancer, 2006, 95, 233–238 http://dx.doi.org/10.1038/sj.bjc.6603227[Crossref]
• [7] Zoller M.E., Rembeck B., Oden A., Samuelsson M., Angervall L., Malignant and benign tumors in patients with neurofibromatosis type 1 in a defined Swedish population, Cancer, 1997, 79, 2125–2133 http://dx.doi.org/10.1002/(SICI)1097-0142(19970601)79:11<2125::AID-CNCR9>3.0.CO;2-N[Crossref]
• [8] National Institutes of Health Consensus Development Conference Statement, Neurofibromatosis, Arch. Neurol. (Chicago), 1988, 45, 575–578
• [9] Ward B.A., Gutmann D.H., Neurofibromatosis 1: from lab bench to clinic, Pediatr. Neurol., 2005, 32, 221–228 http://dx.doi.org/10.1016/j.pediatrneurol.2004.11.002[Crossref]
• [10] Tonsgard J.H., Clinical manifestations and management of neurofibromatosis type 1, Semin. Pediatr. Neurol., 2006, 13, 2–7 http://dx.doi.org/10.1016/j.spen.2006.01.005[Crossref]
• [11] Messiaen L.M., Callens T., Mortier G., Beysen D., Vandenbroucke I., Van Roy N., et al., Exhaustive mutation analysis of the Nf1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects, Hum. Mutat., 2000, 15, 541–555 http://dx.doi.org/10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N
• [12] Jentarra G., Snyder S.L., Narayanan V., Genetic aspects of neurocutaneous disorders, Semin. Pediatr. Neurol., 2006, 13, 43–47 http://dx.doi.org/10.1016/j.spen.2006.01.010[Crossref]
• [13] Gutmann D.H., Wood D.L., Collins F.S., Identification of the neurofibromatosis type 1 gene product, Proc. Natl. Acad. Sci. USA, 1991, 88, 9658–9662 http://dx.doi.org/10.1073/pnas.88.21.9658[Crossref]
• [14] Daston M.M., Scrable H., Nordlund M., Sturbaum AK., Nissen L.M., Ratner N., The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes, Neuron., 1992, 8, 415–428 http://dx.doi.org/10.1016/0896-6273(92)90270-N[Crossref]
• [15] Castle B., Baser M.E., Huson S.M., Cooper D.N., Upadhyaya M., Evaluation of genotype-phenotype correlations in neurofibromatosis type 1, J. Med. Genet., 2003, 40, 109 http://dx.doi.org/10.1136/jmg.40.10.e109[Crossref]
• [16] Trovo-Marqui A.B., Tajara E.H., Neurofibromin: a general outlook. Clin. Genet., 2006, 70, 1–13 http://dx.doi.org/10.1111/j.1399-0004.2006.00639.x[Crossref]
• [17] Weiss B., Bollag G., Shannon K., Hyperactive Ras as a therapeutic target in neurofibromatosis type 1, Am. J. Med. Genet., 1999, 89, 14–22 [Crossref]
• [18] Rasmussen S.A., Overman J., Thomson S.A., Colman S.D., Abernathy C.R., Trimpert R.E., et al., Chromosome 17 loss of heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1, Genes Chromosomes Cancer, 2000, 28, 425–31 http://dx.doi.org/10.1002/1098-2264(200008)28:4<425::AID-GCC8>3.0.CO;2-E[Crossref]
• [19] Sawada S., Florell S., Purandare S.M., Ota M., Stephens K., Viskochil D., Identification of NF1 mutations in both alleles of a dermal Neurofibroma, Nat. Genet., 1996, 14, 110–112 http://dx.doi.org/10.1038/ng0996-110[Crossref]
• [20] Korf B., Malignancy in neurofibromatosis type 1, Oncologist, 2000, 5, 477–485 http://dx.doi.org/10.1634/theoncologist.5-6-477[Crossref]
• [21] Zhu Y., Parada L.F., The molecular and genetic basis of neurological tumours, Nat. Rev. Cancer, 2002, 2, 616–626 http://dx.doi.org/10.1038/nrc866[Crossref]
• [22] Castle B., Baser M.E., Huson S.M., Cooper D.N., Upadhyaya M., Evaluation of genotype-phenotype correlations in neurofibromatosis type 1, J. Med. Genet., 2003, 40, 109 http://dx.doi.org/10.1136/jmg.40.10.e109[Crossref]
• [23] Levy P., Vidaud D., Leroy K., Laurendeau I., Wechsler J., Bolasco G., et al., Molecular profiling of malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1, based on large-scale real-time RT-PCR, Mol. Cancer, 2004, 3, 20 http://dx.doi.org/10.1186/1476-4598-3-20[Crossref]
• [24] Shearer P., Parham D., Kovnar E., Kun L., Rao B., Lobe T., et al., Neurofibromatosis type I and malignancy: review of 32 pediatric cases treated at a single institution, Med. Pediatr. Oncol., 1994, 22, 78–83 http://dx.doi.org/10.1002/mpo.2950220203[Crossref]
• [25] Glover T.W., Stein C.K., Legius E., Andersen L.B., Brereton A., Johnson S., Molecular and cytogenetic analysis of tumors in von Recklinghausen neurofibromatosis, Genes Chromosomes Cancer, 1991, 3, 62–70 http://dx.doi.org/10.1002/gcc.2870030111[Crossref]
• [26] Li Y., O’Connel P., Breidenbach H.H., Cawthon R., Stevens J., Xu G., et al., Genomic organization of the neurofibromatosis 1 gene (NF1), Genomics, 1995, 25, 918 http://dx.doi.org/10.1016/0888-7543(95)80104-T[Crossref]
• [27] Korf B., Malignancy in neurofibromatosis type 1, Oncologist, 2000, 5, 477–485 http://dx.doi.org/10.1634/theoncologist.5-6-477[Crossref]
• [28] Kimura M., Kamata Y., Matsumoto K., Takaya H., Electron microscopical study on the tumour of von Recklinghausen’s neurofibromatosis. Acta. Pathol. Jpn., 1974, 24, 79–91
• [29] Tonsgard J.H., Kwak S.M., Short M.P., Dachman A.H., CT imaging in adults with neurofibromatosis-1: frequent asymptomatic plexiform lesions, Neurology, 1998, 50, 1755–1760 [Crossref]
• [30] Lott I.T., Richardson E.P., Neuropathologic findingsand the biology of neurofibromatosis, Adv. Neuron., 1981, 29, 23–32
• [31] Ferner R.E., Neurofibromatosis 1, Eur. J. Hum. Genet., 2007, 15, 131–8 http://dx.doi.org/10.1038/sj.ejhg.5201676[Crossref]
• [32] DeBella K., Szudek J., Friedman J.M., Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children, Pediatrics, 2000, 105, 608–614 http://dx.doi.org/10.1542/peds.105.3.608[Crossref]
• [33] Evans D.G., Baser M.E., Mc Gaughran J., Sharif S., Howard E., Moran A., Malignant peripheral nerve sheath tumours in neurofibromatosis 1, J. Med. Genet., 2002, 39, 311–314 http://dx.doi.org/10.1136/jmg.39.5.311[Crossref]
• [34] Carli M., Ferrari A., Mattke A., Zanetti I., Casanova M., Bisogno G., et al., Pediatric malignant peripheral nerve sheath tumor: the Italian and German Soft Tissue Sarcoma Cooperative Group, J. Clin. Oncol., 2005, 23, 8422–8430 http://dx.doi.org/10.1200/JCO.2005.01.4886[Crossref]
• [35] Lakkis M.M., Tennekoon G.I., Neurofibromatosis type1. I. General overview, J. Neurosci. Res., 2000, 62, 755–763 http://dx.doi.org/10.1002/1097-4547(20001215)62:6<755::AID-JNR1>3.0.CO;2-W[Crossref]
• [36] Guha A., Lau N., Huvar I., Gutmann D., Provias J., Pawson T., et al., RAS-GTP levels are elevated in human peripheral nerve tumours, Oncogene, 1996, 12, 507–513
• [37] Wu R., Lopez-Correa C., Rutkowski J.L., Baumbach L.L., Glover T.W., Legius E., Germline mutations in NF1 patients with malignancies, Genes Chromosomes Cancer, 1999, 26, 376–380 http://dx.doi.org/10.1002/(SICI)1098-2264(199912)26:4<376::AID-GCC13>3.0.CO;2-O[Crossref]
• [38] Birindelli A., Perrone F., Oggionni M., Lavarino C., Pasini B., Vergani B., et al. Pathway alterations in sporadic and NF1-related malignant peripheral nerve sheath tumours, Lab. Invest., 2001, 81, 833–844 [Crossref]
• [39] De Raedt T., Brems H., Wolkenstein P, Vidaud D., Pilotti S., Perrone F., et al., Elevated risk for MPNST in NF1 microdeletion patient, Am. J. Hum. Genet., 2003, 72, 1288–1292 http://dx.doi.org/10.1086/374821[Crossref]
• [40] Perrone F., Tabano S., Colombo F., Dagrada G., Birindelli S., Gronchi A., et al., p15INK4b, p14ARF and p16INK4a inactivation in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumours, Clin. Cancer Res., 2003, 9, 4132–4138
• [41] Listernick R., Charrow J., Greenwald M., Mets M., Natural history of optic pathway tumors in children with neurofibromatosis type 1: a longitudinal study, J. Pediatr., 1994, 125, 63–66 http://dx.doi.org/10.1016/S0022-3476(94)70122-9[Crossref]
• [42] Listernick R., Louis D.N., Packer R.J., Gutmann D.H, Optic pathway gliomas in children with neurofibromatosis 1: consensus statement from the NF1 Optic Pathway Glioma Task Force, Ann. Neurol., 1997, 41, 143–149 http://dx.doi.org/10.1002/ana.410410204[Crossref]
• [43] Arun D., Gutmann D.H., Recent advances in neurofibromatosis type 1, Curr. Opin. Neuro., 2004, 7, 101–105 http://dx.doi.org/10.1097/00019052-200404000-00004[Crossref]
• [44] Singhal S., Birch J.M., Kerr B., Lashford L., Evans D.G., Neurofibromatosis type 1 and sporadic optic gliomas. Arch. Dis. Child., 2002, 87. 65–70 http://dx.doi.org/10.1136/adc.87.1.65[Crossref]
• [45] Thiagalingam S., Flaherty M., Billson F., North K., Neurofibromatosis type 1 and optic pathway gliomas: follow-up of 54 patients, Ophthalmology, 2004, 111, 568–577 http://dx.doi.org/10.1016/j.ophtha.2003.06.008[Crossref]
• [46] Dasgupta B., Yi Y., Chen D.Y., Weber J.D., Gutmann D.H., Proteomic analysis reveals hyper-activation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumours, Cancer Res., 2005, 1, 2755–2760 http://dx.doi.org/10.1158/0008-5472.CAN-04-4058[Crossref]
• [47] Zhu Y., Harada T., Liu L., Lush M.E., Guignard F., Harada C., et al., Inactivation of NF1 in CNS causes increased glial progenitor proliferation and optic glioma formation, Development, 2005, 132, 5577–5588 http://dx.doi.org/10.1242/dev.02162[Crossref]
• [48] Sung L., Anderson J.R., Arndt C., Raney R.B., Meyer W.H., Pappo A.S., Neurofibromatosis in children with rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study IV, J. Pediatr., 2004, 144, 666–668 http://dx.doi.org/10.1016/j.jpeds.2004.02.026[Crossref]
• [49] Reich S., Overberg-Schmidt S.O., Leenen A., Henze G., Neurofibromatosis 1 associated with embryonal rhabdomyosarcoma of the urinary bladder, Pediatric. Hematol. Oncol., 1999, 16, 263–266 http://dx.doi.org/10.1080/088800199277335[Crossref]
• [50] Lampe A.K., Seymour G., Thompson P.W., Toutain A., Lynch S.A., Familial neurofibromatosis microdeletion syndrome complicated by rhabdomyosarcoma. Arch. Dis. Child., 2002, 87, 444–445 http://dx.doi.org/10.1136/adc.87.5.444[Crossref]
• [51] Jang K.A., Choi J.H., Sung K.J., Moon K.C., Koh J.K., Im D.J., Juvenile chronic myelogenous leukemia, neurofibromatosis 1, and xanthoma, J. Dermatol., 1999, 26, 33–35 [Crossref]
• [52] Benessahraoui M., Aubin F., Paratte F., et al., Juvenile myelomonocytic leukaemia, xanthoma, and neurofibromatosis type 1, Arch. Pediatr., 2003, 10, 891–894. http://dx.doi.org/10.1016/S0929-693X(03)00456-1[Crossref]

Identifiers

DOI

10.2478/s11536-009-0013-x