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.

Identification of a mosaic MTOR variant in purified neuronal DNA in a patient with focal cortical dysplasia using a novel depth electrode harvesting technique

“…Three further studies compared variant allele frequencies (VAFs) of variants identified in resected tissue samples with the VAFs in depth electrode samples from the same patients. [17][18][19] Variants that could be identified in depth electrode samples had 7-27× lower VAFs than in tissue. One explanation for the lower allele frequencies is that only a part of the depth electrode may be located within the area of interest, resulting in a dilution of the sample with healthy cells from other areas.…”

Identification of a novel mosaicMTORvariant in purified neuronal DNA from depth electrodes in a patient with focal cortical dysplasia

“…Ye et al used the same method to identify a mosaic gradient for a KCNT1 variant in a patient with nonlesional multifocal epilepsy 17 . Three further studies compared variant allele frequencies (VAF) of variants identified in resected tissue samples with the VAF in depth electrode samples from the same patients [18][19][20] . Across these studies, variants could be identified in depth electrode samples in four out of five patients.…”