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TSC2 somatic mosaic mutation, including extra-tumor tissue, may be the developmental cause of solitary subependymal giant cell astrocytoma

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Abstract

Purpose

Subependymal giant cell astrocytomas (SEGAs) are tumors that usually arise in the wall of one or the other lateral ventricle near a foramen of Monro, most often on a background of tuberous sclerosis complex (TSC). TSC has a variety of clinical manifestations caused by germline mutations of the TSC complex subunit 1 or 2 (TSC1, TSC2) genes. SEGAs without clinical manifestations of TSC are termed solitary SEGAs, which are hypothesized to be caused by tumor-only TSC1/2 mutations, or “forme fruste” of TSC with somatic mosaic mutations. However, it is difficult to distinguish between the two. Here, we report three patients with genetically investigated solitary SEGAs and review this rare manifestation.

Methods

SEGA was completely removed in two patients and partially removed in one. Genetic analyses were performed on the tumor tissue and on peripheral blood via DNA microarray, reverse-transcriptase polymerase chain reaction, and next-generation sequencing with ultra-deep sequencing of mutation points.

Results

All three patients had tumors with TSC2 somatic mutations and loss of heterozygosity (LOH). In one patient, the same TSC2 mutation was also detected in 1% of leukocytes in his blood. The tumors did not recur, and clinical manifestations of TSC did not develop during the 4-year follow-up.

Conclusions

The genetic cause of solitary SEGAs may be a TSC2 mutation with LOH. In patients with solitary SEGA, mosaic mutations may present in other organs, and TSC may clinically manifest later in life; therefore, patients should be followed up for prolonged periods.

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Acknowledgements

We thank Drs. Kosuke Nakajo, Shugo Nishijima, Yuta Tanoue, Toshiyuki Kawashima, and Naohiro Yamamoto for their help with clinical evaluations and patients’ care.

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Authors and Affiliations

  1. Department of Neurosurgery, Osaka City University Graduate School of Medicine, Osaka, Japan

    Tsuyoshi Sasaki, Takehiro Uda & Takeo Goto

  2. Department of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan

    Ichiro Kuki & Shin Okazaki

  3. Department of Pediatric Neurosurgery, Osaka City General Hospital, Osaka, Japan

    Noritsugu Kunihiro

  4. Center for Clinical Genomics, Kanazawa Medical University Hospital, Kanazawa, Japan

    Yo Niida

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  1. Tsuyoshi Sasaki
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  2. Takehiro Uda
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Correspondence to Takehiro Uda.

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Sasaki, T., Uda, T., Kuki, I. et al. TSC2 somatic mosaic mutation, including extra-tumor tissue, may be the developmental cause of solitary subependymal giant cell astrocytoma. Childs Nerv Syst 38, 77–83 (2022). https://doi.org/10.1007/s00381-021-05399-y

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