A Case of Solitary Subependymal Giant Cell Astrocytoma

Abstract

Subependymal giant cell astrocytoma (SEGA) is a unique brain tumor arising in tuberous sclerosis complex (TSC), an autosomal dominant inherited phacomatosis. There are several case reports of solitary SEGA without any other manifestations of TSC. Usually these cases are thought to be forme fruste of TSC due to somatic mosaicism. However, no previous reports have used molecular methodology to fully investigate mutations in TSC genes or the possibility of somatic mosaicism. Here, we report a 20-year-old woman with a brain tumor. Pathological diagnosis was consistent with SEGA, but comprehensive clinical screening found no other lesions indicative of TSC. Molecular analysis of the tumor revealed loss of heterozygosity and allelic mutation (5228G>A, R1743Q) of TSC2. To detect the small fraction of mosaic mutation in somatic cells, we developed a highly sensitive new method: triple-nested polymerase chain reaction-restriction fragment length polymorphism. The identical TSC2 missense mutation was not detected in any other tissues from the same patient, including peripheral blood, buccal mucosa, urinary sediment, nail, and hair. According to these results, this patient should be considered as having SEGA that developed from two somatic hit mutations in TSC2, rather than being a TSC2 patient with a very small fraction of somatic mosaicism.

Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model

“…Similar alterations in sEPSC kinetics were observed in ‘double-hit’ Tsc1 mutant mice. In a recent study, using in utero electroporation and relying on the «second-hit» mutation concept 36 , Bordey and co-workers 15 generated a Tsc1 −/− animal model with the hallmark of human TSC, namely the tubers. We used this model to test the impact of a «second-hit» mutation on functional upregulation of slow NMDARs.…”

Subependymal giant cell astrocytoma in the absence of tuberous sclerosis: illustrative case

“…SEGA in the absence of phenotypic or genotypic TSC is an exceedingly rare phenomenon. The first case was reported by Ichikawa et al in 2005, 15 followed by 5 other cases (Table 2). 7,[16][17][18][19] Tompe et al 7 discussed a case of a 17-year-old male without TSC who had an extraventricular SEGA located in the occipital lobe.…”

Multiparameter Quantitative Analyses of Diagnostic Cells in Brain Tissues from Tuberous Sclerosis Complex

“…While probable BCs could still be highlighted in the experimental samples described here, the probability threshold (i.e., the level of certainty when identifying probable BCs) was lower when staining or image quality was affected by experimental variation. In future, it will be of interest to determine if this approach can be extended to reliably identify cells of interest for applications such as laser-capture microdissection, which has been used to address the question of whether TSC1/2 loss of heterozygosity (LOH) occurs in BCs and / or other cells found within epileptic foci (Ichikawa et al, 2005; Giannikou et al, 2016; Bongaarts et al, 2017; D’Gama et al, 2017; Blair et al, 2018; Baldassari et al, 2019; Eichmuller et al, 2022).…”