Gliomas in people with NF1 show alterations in the RAS/MAPK pathway, generally in the absence of BRAF alterations (common to sporadic pilocytic astrocytomas) or IDH or histone H3 mutations (common to diffuse gliomas subsets).
In the present study we searched for FGFR1-ITD by droplet digital PCR (DDPCR™) and for FGFR1 point mutations by HRM-sequencing in a series of formalin-fixed paraffin-embedded (FFPE) LGNTs including 12 DNT, 2 oligodendrogliomas lacking IDH mutation and 1p/19q co- deletion (pediatric-type oligodendrogliomas; PTOs), 3 pediatric diffuse astrocytomas (PDAs), 14 gangliogliomas (GGs) and 5 pilocytic astrocytomas (PAs).
Among glioma subtypes, activating FGFR1 alterations have been observed in a subpopulation of pilocytic astrocytomas while FGFR3 fusions occur in IDH wild-type diffuse gliomas, resulting in high FGFR3 protein expression.
A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival.
This study identified the expression of KIAA1549-BRAF fusion gene and BRAF V600E mutation, mutations at exon 4 of the IDH1 and IDH2 genes in samples of pilocytic astrocytomas (PA) and grade-II astrocytomas (A-II) pediatric patients.
Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations.
Different molecular biomarkers were identified by genetic studies and some of these are used in neuro-oncology for the evaluation of glioma patients, in particular combined deletions of the chromosome arms 1p and 19q in oligodendroglial tumors, methylation status of the O-6 methylguanine- DNA methyltransferase gene promoter and alterations in the epidermal growth factor receptor pathway in adult malignant gliomas, isocitrate dehydrogenase 1 (IDH1) and IDH2 gene mutations in diffuse gliomas, as well as BRAF status in pilocytic astrocytomas.
This review summarizes recent studies on diagnostic and prognostic markers in gliomas such as the BRAF fusion gene in pilocytic astrocytomas and 1p/19q codeletion, O-6-methylguanine-DNA methyltransferase status and isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations in diffuse gliomas.