Disease relevance of Neurofibrosarcoma

• Neurofibromatosis type 1 (NF1), a common autosomal dominant disorder caused by loss of the NF1 gene, is characterized clinically by neurofibromas and more rarely by neurofibrosarcomas [1].
• Although all cells in either the neurofibrosarcoma or Schwannoma cultures appeared morphologically similar (suggesting homogeneity), apolipoprotein E was immunochemically detected in the perinuclear region of only half of the cells [2].
• Frequent activation of the Ki-ras oncogene at codon 12 in N-methyl-N-nitrosourea-induced rat prostate adenocarcinomas and neurogenic sarcomas [3].
• Apolipoprotein E synthesis in neurofibrosarcoma and schwannoma cell cultures from two individuals with neurofibromatosis [2].
• Histologically these neurogenic tumours show a manifold picture; in addition to spindle-cell sarcomas pleomorphic structures are to be found, which can be similar to rhabdomyo-, lipo-, chondro-, angio-, or osteogenic sarcomas so that a histological diagnosis of a neurogenic sarcoma cannot always be made without clinical details [4].

High impact information on Neurofibrosarcoma

• Both neurofibrosarcomas from patients with "atypical" NF and 5 of 6 neurofibrosarcomas from NF1 patients displayed loss of alleles for polymorphic DNA markers on chromosome 17 [5].
• In a preliminary search for p53 aberrations by direct sequencing of polymerase chain reaction-amplified DNA from 7 neurofibrosarcomas, 2 tumors that contained point mutations in exon 4 of the p53 gene were found, suggesting a role for this gene in at least some neurofibrosarcomas [5].
• Inhibiting VEGF function may therefore be a useful adjuvant therapy for neurogenic sarcomas [6].
• Inhibition of angiogenesis by blocking activation of the vascular endothelial growth factor receptor 2 leads to decreased growth of neurogenic sarcomas [6].
• Neurofibromin, the gene product of NF1, is a Ras GTPase Activating Protein. The absence of neurofibromin leads to increased levels of Ras-GTP, which contributes to the proliferation of NF1 neurogenic sarcoma cell lines [7].

Chemical compound and disease context of Neurofibrosarcoma

• Neurofibrosarcoma growth after 6 weeks of AGM-1470 treatment was only 8.5% of the growth found in the control animals (p < 0.01) [8].
• Inhibition of growth and angiogenesis of human neurofibrosarcoma by heparin and hydrocortisone [9].
• A periocular neurofibrosarcoma was debulked and treated with intralesional cisplatin in a 5-year-old Thoroughbred mare [10].
• Treatment of a large high-grade neurofibrosarcoma with concomitant vinblastine, doxorubicin, and radiotherapy [11].

Biological context of Neurofibrosarcoma

• Thus the formation of malignant neurofibrosarcomas may result from several independent genetic events including mutation of the NF1 gene, whose mechanism of tumorigenesis remains uncertain, and subsequent loss of a "tumor suppressor" gene on 17p, most likely p53 [5].
• Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma [12].
• Aberrant CpG island methylation in neurofibromas and neurofibrosarcomas [13].

Anatomical context of Neurofibrosarcoma

• Neurofibromatosis type 1 (NF1) is characterized by the formation of neurofibromas, benign tumors of the peripheral nerve consisting essentially of Schwann cells, which can sometimes turn malignant to form neurofibrosarcomas [14].

Gene context of Neurofibrosarcoma

• Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma [12].
• The neurofibrosarcoma was negative for TPA and CEA [15].
• In this case report, the authors document a retroperitoneal neurogenic sarcoma occurring in a 20-year-old woman with NF2 (bilateral acoustic schwannomas, meningioma, and multiple intraspinal tumors) [16].
• N-myc showed a low level of expression in one neurofibrosarcoma and a neurofibroma, and a higher level of expression in a second neurofibrosarcoma (and in this same subject's skin and nerve) [17].
• In this study, the vascularity, vascular endothelial growth factor (VEGF) expression, and effects of inhibiting VEGF receptor on growth of neurogenic sarcomas were examined [6].

References