Neurofibromatosis type 1 associated low grade gliomas: A comparison with sporadic low grade gliomas. (August 2016)

• Record Type: Journal Article
• Authors: Helfferich, Jelte; Nijmeijer, Ronald; Brouwer, Oebele F.; Boon, Maartje; Fock, Annemarie; Hoving, Eelco W.; Meijer, Lisethe; den Dunnen, Wilfred F.A.; de Bont, Eveline S.J.M.
• Is Part Of: Critical reviews in oncology/hematology. Volume 104(2016)
• Page Start: 30
• Page End: 41
• Publication Date: 2016-08
• Subjects: NF1 neurofibromatosis type 1 -- LGG low grade glioma -- MAPK mitogen activated protein kinase -- mTOR mammalian target of rapamycin -- PA pilocytic astrocytoma -- MPNST malignant peripheral nerve sheath tumours -- GAP GTPase-activating protein -- RB retinoblastoma -- GFAP glial fibrillary acid protein -- OPG optic pathway glioma -- JNK c-Jun-Nh2-kinase -- FTI Farnestyltransferase inhibitors; Neurofibromatosis -- NF1 gene -- BRAF:KIAA1549 fusion -- Low grade glioma -- Pilocytic astrocytoma; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2016.05.008
• Languages: English
• ISSNs: 1040-8428

Abstract

Abstract: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, associated with a variable clinical phenotype including café-au-lait spots, intertriginous freckling, Lisch nodules, neurofibromas, optic pathway gliomas and distinctive bony lesions. NF1 is caused by a mutation in the NF1 gene, which codes for neurofibromin, a large protein involved in the MAPK- and the mTOR-pathway through RAS-RAF signalling. NF1 is a known tumour predisposition syndrome, associated with different tumours of the nervous system including low grade gliomas (LGGs) in the paediatric population. The focus of this review is on grade I pilocytic astrocytomas (PAs), the most commonly observed histologic subtype of low grade gliomas in NF1. Clinically, these PAs have a better prognosis and show different localisation patterns than their sporadic counterparts, which are most commonly associated with a KIAA1549:BRAF fusion. In this review, possible mechanisms of tumourigenesis in LGGs with and without NF1 will be discussed, including the contribution of different signalling pathways and tumour microenvironment. Furthermore we will discuss how increased understanding of tumourigenesis may lead to new potential targets for treatment.