Characterization of low-grade epilepsy-associated tumor from implanted stereoelectroencephalography electrodes

Abstract

Low-grade epilepsy-associated tumors (LEATs) are a common cause of drug-resistant epilepsy in children. Herein, we demonstrate the feasibility of using tumor tissue derived from stereoelectroencephalography (sEEG) electrodes upon removal to molecularly characterize tumors and aid in diagnosis. An 18-year-old male with focal epilepsy and MRI suggestive of a dysembryoplastic neuroepithelial tumor (DNET) in the left posterior temporal lobe underwent implantation of seven peri-tumoral sEEG electrodes for peri-operative language mapping and demarcation of the peri-tumoral ictal zone prior to DNET resection. Using electrodes that passed through tumor tissue, we show successful isolation of tumor DNA and subsequent analysis using standard methods for tumor classification by DNA, including Glioseq targeted sequencing and DNA methylation array analysis. This study provides preliminary evidence for the feasibility of molecular diagnosis of LEATs or other lesions using a minimally invasive method with microscopic tissue volumes. The implications of sEEG electrodes in tumor characterization are broad but would aid in diagnosis and subsequent targeted therapeutic strategies.

Keywords: LEATs; methylation; mutation; sEEG.

FIGURE 1

Use of sEEG electrode isolated DNA for Glioseq mutation analysis. (A) T2‐weighted MR image demonstrating relationship of electrode contacts to tumor, highlighting only the electrodes used for this study. (B) 3D renderings of 7 electrode trajectories with tumoral mask. (C) Measurement of isolated DNA from sEEG electrodes and resected tumor tissue. (D) Glioseq mutations detected in sEEG electrode isolated DNA and biopsy resected tissue DNA with allelic frequencies.

FIGURE 2

Use of methylation tumor classification to identify class and copy number variation in sEEG electrode isolated DNA. (A) Methylation classification of sEEG electrode isolated DNA. (B) Copy number analysis in isolated tumor DNA. (C) Gene map of chromosome 2q12.3 via integrated genomics viewer. (D) qPCR CNV analysis of BUB1, a gene embedded in chromosome 2q12.3 in prime DNA versus control normal human astrocyte (NHA) cell culture line.**P = 0.0072. Data were normalized to RNAseP housekeeping gene (known to have 1 copy).