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JMD 2005, Vol. 7, No. 4
Copyright © 2005 American Society for Investigative Pathology & Association for Molecular Pathology

A Case of Solitary Subependymal Giant Cell Astrocytoma

Two Somatic Hits of TSC2 in the Tumor, without Evidence of Somatic Mosaicism

Tomotsugu Ichikawa^*, Akiko Wakisaka, Shigeru Daido^*, Soichiro Takao^*, Takashi Tamiya, Isao Date^*, Shoichi Koizumi and Yo Niida

From the Department of Neurological Surgery, * Okayama University Graduate School of Medicine and Dentistry, Okayama; the Department of Pediatrics, Kanazawa University Graduate School of Medical Science, Ishikawa; and the Department of Neurological Surgery, Kagawa University School of Medicine, Kagawa, Japan

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.

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