Neurofibromatosis type 1 associated low grade gliomas: A comparison with sporadic low grade gliomas.
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.
Department of Paediatrics, Beatrix Children's Hospital, Paediatric Oncology/Hematology Division, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Neurology, Paediatric Neurology Division, University Medical Center Groningen, University of Groningen, The Netherlands.
Jelte
J
Helfferich
Department of Pathology and Medical Biology, Pathology Division, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ronald
R
Nijmeijer
Department of Neurology, Paediatric Neurology Division, University Medical Center Groningen, University of Groningen, The Netherlands.
Oebele F
OF
Brouwer
Department of Neurology, Paediatric Neurology Division, University Medical Center Groningen, University of Groningen, The Netherlands.
Maartje
M
Boon
Department of Neurology, Paediatric Neurology Division, University Medical Center Groningen, University of Groningen, The Netherlands.
Annemarie
A
Fock
Department of Neurosurgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Eelco W
EW
Hoving
Department of Paediatrics, Beatrix Children's Hospital, Paediatric Oncology/Hematology Division, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Lisethe
L
Meijer
Department of Pathology and Medical Biology, Pathology Division, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Wilfred F A
WF
den Dunnen
Department of Paediatrics, Beatrix Children's Hospital, Paediatric Oncology/Hematology Division, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: e.s.j.m.de.bont@umcg.nl.
Eveline S J M
ES
de Bont
D000818:Animals; D005910:Glioma / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D009154:Mutation; D060787:Neoplasm Grading; D009456:Neurofibromatosis 1 / Q000150:complications*; D010641:Phenotype; D015398:Signal Transduction; D059016:Tumor Microenvironment
BRAF:KIAA1549 fusion; Low grade glioma; NF1 gene; Neurofibromatosis; Pilocytic astrocytoma