A BRAFV600E mutation and homozygous deletion of CDKN2A/B were observed, which is similar to the genetic features of PXA or epithelioid glioblastoma, but the additional loss of ATRX nuclear immunoreactivity and absence of TERT promoter mutation were unusual findings, indicating a novel genetic profile.
Because mutations of FANCA and BRAF and copy number variations of CDKN2A/B are more frequent in PXA than in glioblastoma, they might be used to distinguish the 2 tumors.
The authors treated 4 BRAFV600E patients, each with a different type of primary brain tumor (pilocytic astrocytoma, papillary craniopharyngioma, ganglioglioma, and pleomorphic xanthoastrocytoma) with the combination of dabrafenib and trametinib.
The efficacy of bevacizumab, temozolomide, lomustine (CCNU), irinotecan (CPT 11), a tyrosine kinase inhibitor (sorafenib), a selective MEK1/2 inhibitor (cobimetinib), and a BRAF inhibitor (vemurafenib) were assessed in two subcutaneous xenografts: D645 PXA (V600E-mutant) and D2363 PXA (V600E-non-mutant) (n = 5-10 mice).
In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8<sup>+</sup> tumor-infiltrating lymphocytes, and longer survival with the addition of BEV.
The ability of the polio: rhinovirus recombinant, PVSRIPO, to infect PXA (645 [BRAFV600E mutation], 2363) and medulloblastoma (D283, D341) cells were determined by viral propagation measurement and cell proliferation.
BRAF mutations are most frequently detected in certain subtypes of low-grade glioma, such as pilocytic astrocytoma (PA), pleomorphic xanthoastrocytoma (PXA), ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNT).
Specifically, both the initial and recurrent tumors of the patient showed the same BRAFV600E mutation, which refutes previous suggestions that BRAF mutations may be limited to intracranial PXAs and also shows that BRAF mutations may occur earlier in PXA tumorigenesis.
In summary, we showed that PLGG tumorigenicity was low despite the presence of putative CSCs, and our data supported GFAP<sup>-</sup>/Vimentin<sup>+</sup> cells, <i>CDKN2A</i> homozygous deletion in trisomy chromosome 9 cells, and <i>BRAF V600E</i> mutation as candidate drivers of tumor progression in the PXA xenografts.
Both components were positive for the mutant IDH1 R132H and showed loss of ATRX expression, whereas BRAFV600E was restricted to the PXA-like component.
BRAFV600E mutations are found frequently in circumscribed low-grade gliomas such as pleomorphic xanthoastrocytoma (PXA) and extra-cerebellar pilocytic astrocytoma, or epithelioid glioblastomas (E-GBM), a rare variant of GBM.
Our data indicate, that in addition to the histological and immunohistochemical evaluation, investigation of MGMT promoter methylation and in particular BRAFV600E mutations represent reliable additional tools to sustain differentiation of gcGBM from PXA on a molecular basis.
The BRAFV600E mutation occurs frequently in certain brain tumors such as pleomorphic xanthoastrocytoma, ganglioglioma, and pilocytic astrocytoma, and less frequently in epithelioid and giant cell glioblastoma.
Prognostic significance of histological anaplasia and BRAFV600E mutation were retrospectively evaluated in 74 patients with pleomorphic xanthoastrocytoma (PXA).
Although this glioma was difficult to clarify, diagnosis of pleomorphic xanthoastrocytoma with anaplastic feature was suggested based on the association of some pathological feature (eosinophilic granular bodies, reticulin network and diffuse CD34 expression) and the BRAFV600E mutation.
We evaluated the immunohistochemical (IHC) detection of BRAFV600E mutation in PXA by comparing to gold standard molecular analysis and investigating the interobserver variability of the IHC scoring.