Disease relevance of Neurofibroma

• Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with a high mutation rate and variable expression, characterized by neurofibromas, café-au-lait spots, Lisch nodules of the iris, and less frequent features including bone deformities and learning disabilities [1].
• Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1 [2].
• We observed varying levels of NF1 mRNA editing in different tumors, with a higher range of editing levels in more malignant tumors (e.g., neurofibrosarcomas) compared to benign tumors (cutaneous neurofibromas) [3].
• It was detectable in all of the human tumor tissues tested (NF1 neurofibroma, sporadic intramedullar neurinoma, sporadic meningiomas, NF2 schwannoma, NF2 meningioma, basalioma, and naevus) as well as in cultured tumor cell lines and cultured primary cells [4].
• The characteristics of NF1, which include cafe-au-lait spots, neurofibromas, Lisch nodules, optic glioma, osseous lesions, macrocephaly, short stature and mental retardation suggest that the genetic lesion affects the proper development of multiple organ systems [5].

High impact information on Neurofibroma

• Mitotic recombination effects homozygosity for NF1 germline mutations in neurofibromas [6].
• Unlike humans, mice that are heterozygous for a mutation in Nf1 do not develop neurofibromas [7].
• These Schwann cells are found both in association with axons and in the extracellular matrix that is prevalent in neurofibromas, and in which fibroblasts are also abundant [8].
• Recently, somatic loss of heterozygosity (LOH) has been described for neurofibromas, and mutations in both copies of the NF1 gene have been reported for a dermal neurofibroma [9].
• Schwann cells harbor the somatic NF1 mutation in neurofibromas: evidence of two different Schwann cell subpopulations [10].

Chemical compound and disease context of Neurofibroma

• We hypothesize that progesterone may play an important role in neurofibroma growth and suggest that antiprogestins may be useful in the treatment of this tumor [11].
• Treatment of the cultures with 0.1 mM cyclic adenosine 3'5'-monophosphate (cAMP) analogue, 8-bromo cAMP, caused marked inhibition of proliferation of both SLCs and FLCs derived from all 6 neurofibromas [12].
• To investigate histogenesis of neurofibroma, early lesions of N-nitroso-N-ethylurea-induced neurofibroma of Syrian golden hamsters were examined [13].
• Neurofibromas: location by scanning with Tc-99m DTPA. Work in progress [14].
• The adjacent tissue showed wavy, spindle-shaped cells and collagen fibers in a myxoid stroma rich in hyaluronic acid, a pattern reminiscent of neurofibroma [15].

Biological context of Neurofibroma

• Pure populations of neurofibroma-derived Schwann cells bearing both NF1 mutated alleles (NF1-/-) have been isolated from different neurofibromas showing loss of heterozygosity of nearly the entire 17q chromosome [6].
• Our results suggest that small subtle mutations occur with similar frequency to that of LOH in benign neurofibromas and that somatic inactivation of the NF1 gene is a general event in these tumors [2].
• Point mutations of the transmembrane domain coding region of the neu proto-oncogene in N-nitroso-N-ethylurea-induced hamster neurofibromas were found at high frequency (93%; 14 of 15) [16].
• We analyzed 5 dinucleotide repeat loci in DNAs from neurofibromas and matched normal skin from 16 NF1 patients [17].
• Two tumor types that have been linked to specific gene alterations are schwannomas, which have mutations in the neurofibromatosis (NF) type 2 (NF2) gene, and neurofibromas, which characteristically possess NF type 1 (NF1) gene mutations [18].

Anatomical context of Neurofibroma

• Recent evidence demonstrates that somatic mutations at the NF1 gene are found in neurofibromas, but it has not been demonstrated whether SCs, fibroblasts and/or both cell types bear a somatic loss of NF1 [10].
• Because nerve growth factor-like activity may be present in neurofibromas and the cells comprising neurofibromas are neural crest derivatives, we have investigated whether nerve growth factor (NGF) receptors are present on cells from dissociated dermal neurofibromas [19].
• Immunoblotting also revealed positive expression of the 250-kd NF1 gene product in the brain, the normal peripheral nerves, and 7 of 14 ENU-induced neurofibromas [20].
• Using the peroxidase-antiperoxidase immunohistochemical method S-100 was also found in tumors derived from Schwann cells and melanocytes, including neurofibromas, neurilemomas, granular cell myoblastomas, cutaneous nevi, and malignant melanomas [21].
• Schwannomas (86%), neurofibromas (100%) and meningiomas (86%) showed CA C positivity of the tumor cells, as did choroid plexus papillomas and gangliogliomas [22].

Gene context of Neurofibroma

• In contrast, mitogenic activity present in normal human adult nerves and in neurofibromas from patients with type 1 neurofibromatosis analyzed in the absence of forskolin is largely inhibitable by anti-HGF [23].
• Compared to normal nerves, schwannomas express higher total levels of CD44 and additional splice variants, whereas CD44 expression in neurofibromas is unaltered [18].
• The data support a possible central role for MK as a mediator of angiogenesis and neurofibroma growth in NF1 [24].
• Here we show that FK is constitutively expressed by skin endothelial cells, dermal dendrocytes and cells within neurofibromas [25].
• GFAP was expressed by 33% of the benign schwannomas, 40% of the neurofibromas, and 7% of the malignant schwannomas [26].

Analytical, diagnostic and therapeutic context of Neurofibroma

• Western blot analysis failed to detect full-length neurofibromin in any of the neurofibroma SC cultures, indicating that neurofibromin-deficient SCs had a substantial growth advantage [27].
• The distribution and nature of extracellular matrix proteins in neurofibroma tissue was studied by indirect immunofluorescence, immunoelectron microscopy, immunoblotting, and rotary shadowing [28].
• Single photon emission computed tomography (SPECT) was used to study uptake of technetium-99m diethylenetriaminepentaacetic acid ([99mTc]DTPA) by para-axial neurofibromas in 13 patients [29].
• METHODS: By means of immunohistochemistry, the presence of GHRs was investigated in two groups of patients: 16 patients without NF1 with solitary neurofibromas (group A) and 10 patients with NF1 with localised neurofibromas (group B) [30].
• In the present study we observed that human Schwann cells and cutaneous neurofibroma Schwann cell cultures secreted abundant MMP-3 and their proliferation was inhibited by autologous and rat Schwann cell conditioned media [31].

References