Role of DNA Methylation Profile in Diagnosing Astroblastoma: A Case Report and Literature Review

Abstract

Astroblastoma is a rare tumor of the central nervous system (CNS) with uncertain clinical behavior. Recently, DNA methylation profiling has been shown to provide a highly robust and reproducible approach for the classification of all CNS tumors across different age groups. By using DNA methylation profiling, a subset of CNS high-grade tumors with astroblastoma-like morphology characterized by the meningioma 1 gene (MN1) rearrangements, has been identified; they were termed "CNS high-grade neuroepithelial tumors with MN1 alteration" (CNS-HGNET-MN1). Here, we describe a case of CNS-HGNET-MN1 diagnosed by DNA methylation profiling, using Illumina Infinium HumanMethylationEPIC BeadChip (EPIC), that offers the opportunity to conduct a brief literature review. The patient presented with an episode of partial seizures involving the right hemisoma. A gross total resection was performed. No other treatment was proposed in light of the histological and molecular findings. After 21 months, the patient is disease-free in good clinical conditions. Also in view of this case, we recommend DNA-methylation profiling as an important tool for diagnosis and more effective patient stratification and management.

Keywords: CNS-HGNET-MN1; DNA methylation profiling; astroblastoma; brain tumor; next-generation sequencing.

FIGURE 1

MRI – Axial images. (A) T2W image shows a heterogeneous mass in the left parietal lobe with characteristic multicystic bubbly appearance. (B,C) There are mild peritumoral edema on FLAIR image and diffusion restriction on ADC. (D) No sign of hyperperfusion on dynamic susceptibility-weighted MRI. (E) The T1W post-contrast image shows strong contrast-enhancement of the lesion. (F) Post-contrast-enhanced cerebral MRI performed 20 months after surgery shows no evidence of recurrent/residual disease.

FIGURE 2

Histology – The tumor was composed of elongated cells with abundant eosinophilic cytoplasm and tapered processes, radiating from the vessels and forming characteristic astroblastic rosettes throughout (A: HE 10x, B: HE 20x). Sclerosing vessels with scattered foamy histiocytes were present (C: HE 20x). Focally, ribbon-like (D: HE 40x) or fusiform patterns were observed (E: HE 40x). A few highly cellular areas with moderate cellular pleomorphism were noticed (F: HE 20x).

FIGURE 3

MDS (multidimensional scaling) analysis performed on the 1000 most variable probes of the whole genome DNA methylation data shows a close similarity between our case (OPBG) and CNS-HGNET-MN1, while it clearly separates from other CNS-HGNET. Color legend of the MDS plot as follows: Astroblastoma case (black); CNS-NB-FOXR2 (blue); EFT-CIC (violet); HGNET-MN1 (pink); HGNET-BCOR (light green).

FIGURE 4

Copy number variation profile – Depiction of chromosome 1 to 22 and X. Gains/amplifications represent positive (green), losses negative (red) deviations from the baseline. 29 brain tumor relevant genomic regions are highlighted. The presented case showed losses of chromosome X and multiple deletions near the MN1 locus on 22q12.1.