DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma

Abstract

BackgroundPleomorphic xanthoastrocytoma (PXA) is a rare WHO grade II tumor accounting for less than 1% of all astrocytomas. Malignant transformation into PXA with anaplastic features, is unusual and correlates with poorer outcome of the patients.MethodsUsing a DNA methylation custom array, we have quantified the DNA methylation level on the promoter sequence of 807 cancer-related genes of WHO grade II (n = 11) and III PXA (n = 2) and compared to normal brain tissue (n = 10) and glioblastoma (n = 87) samples. DNA methylation levels were further confirmed on independent samples by pyrosequencing of the promoter sequences.ResultsIncreasing DNA promoter hypermethylation events were observed in anaplastic PXA as compared with grade II samples. We further validated differential hypermethylation of CD81, HCK, HOXA5, ASCL2 and TES on anaplastic PXA and grade II tumors. Moreover, these epigenetic alterations overlap those described in glioblastoma patients, suggesting common mechanisms of tumorigenesis.ConclusionsEven taking into consideration the small size of our patient populations, our data strongly suggest that epigenome-wide profiling of PXA is a valuable tool to identify methylated genes, which may play a role in the malignant progression of PXA. These methylation alterations may provide useful biomarkers for decision-making in those patients with low-grade PXA displaying a high risk of malignant transformation.

Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, and Epithelioid Glioblastoma: Case Series With Clinical Characteristics, Molecular Features and Progression Relationship

“…IDH1 and TP53 mutations are usually not detected in A-PXA and E-GBM [16][17][18][19][20][21][22]. Comprehensive immunohistochemistry and NGS panel results showed that our case did not contain mutations in these genes in A-PXA and E-GBM, indicating that these genes did not affect the progression from A-PXA to E-GBM.…”

“…E-GBM may coexist with PXA [14] and a case report of E-GBM arising from a PXA has recently been reported, but the relationship between E-GBM and malignant progression in PXA requires further clari cation [15]. PXA, A-PXA, and E-GBM show overlapping features, for example, BRAF V600E mutant, IDH1 wild-type, TP53 wild-type, etc [16][17][18][19][20][21][22]. In addition, there are overlapping histological features among E-GBM, PXA, and A-PXA, such as discohesive epithelioid patterns of tumor cells, perivascular and intercellular lymphocyte in ltration.…”

Anaplastic pleomorphic xanthoastrocytoma with disseminated growth pattern at the time of diagnosis as well as after treatment: case report and review of literature

“…Others, including 2 anaplastic PXA cases, were found to be unmethylated. In another study, Martínez et al [18] investigated the differences in DNA methylation alterations between conventional PXA and anaplastic PXA. They found that promoter hypermethylation of HOXA5, CD81, ASCL2, HCK and TES genes in anaplastic PXA cases was comparable to that in conventional PXA [18].…”

“…In another study, Martínez et al [18] investigated the differences in DNA methylation alterations between conventional PXA and anaplastic PXA. They found that promoter hypermethylation of HOXA5, CD81, ASCL2, HCK and TES genes in anaplastic PXA cases was comparable to that in conventional PXA [18]. However, all these findings need to be confirmed in larger sample based studies to identify clinically relevant biomarkers and guide treatment of anaplastic PXA.…”

“…1a-d). Positron emission tomography-computed tomography (PET-CT) demonstrated intense 18 F-fluorodeoxyglucose (FDG) and 11 C-methionine (MET) uptake in the left temporal lesion, suggesting an aggressive neoplasm ( Fig. 1e and f).…”