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Identification of TSC1 or TSC2 mutation limited to the tumor in three cases of solitary subependymal giant cell astrocytoma using next-generation sequencing technology

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Abstract

Purpose

Subependymal giant-cell astrocytomas (SEGAs) are low grade intraventricular tumors typically found in patients with tuberous sclerosis complex (TSC). The occurrence of SEGA in non TSC patients is very rare and from a genetic point of view these so-called solitary SEGA are thought to result either from somatic mutations in one of the TSC genes (TSC1 or TSC2) limited to the tumor, or be part of a “forme fruste” of TSC with somatic mosaicism. We report on three new cases of solitary SEGA with germline and somatic mutation analysis.

Methods

We retrospectively analyzed TSC genes in three patients with a solitary SEGA using next-generation sequencing technique.

Results

In the three patients, a somatic mutation of TSC1 or TSC2 was found only in the tumor cells: one patient had a TSC1 heterozygote mutation, involving the natural acceptor splicing site of intron 15 (c.1998-1G > A (p.?). Two patients had a TSC2 mutation located in the canonical splicing donor site of intron 5 (c.599 + 1G > A) in 70% of the alleles in one patient and in exon 9: c.949_955dup7 (p.V319DfxX21) in 25 of the alleles in the second patient. No other TSC mutations were found in patient’s blood or tumor and those identified mutations were absent in blood DNA from parents and siblings.

Conclusion

We therefore conclude that solitary SEGA can occur with a TSC1 or TSC2 mutation limited to the tumor in patients without TSC.

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Authors and Affiliations

  1. Service de neurochirurgie pediatrique, Foundation Rothschild Hospital, Paris, France

    Martine Fohlen & Georg Dorfmüller

  2. Service de Génétique Clinique, Chromosomique et Moléculaire, Centre de Compétence des Epilepsies rares (CReER), CHU-Hôpital Nord, Saint Etienne, France

    Ines Harzallah & Renaud Touraine

  3. Service d’anatomie et cytologie pathologiques, Hôpital Lariboisière, Paris, France

    Marc Polivka

  4. Service de génétique, Centre Hospitalier Universitaire, Nice, France

    Fabienne Giuliano

  5. Service de Génétique, Centre de Référence des Épilepsies Rares (CReER), Hôpital Femme Mère Enfant, Bron, France

    Linda Pons

  6. Centre de Pathologie et Neuropathologie Est, Hospices Civils de Lyon; Université Claude Bernard Lyon1, Lyon, France

    Nathalie Streichenberger

  7. Institut NeuroMyogène, CNRS UMR 5310-INSERM U1217, Villeurbanne, France

    Nathalie Streichenberger

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  1. Martine Fohlen
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Correspondence to Martine Fohlen.

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Fohlen, M., Harzallah, I., Polivka, M. et al. Identification of TSC1 or TSC2 mutation limited to the tumor in three cases of solitary subependymal giant cell astrocytoma using next-generation sequencing technology. Childs Nerv Syst 36, 961–965 (2020). https://doi.org/10.1007/s00381-020-04551-4

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  • DOI: https://doi.org/10.1007/s00381-020-04551-4

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