title: A case of solitary subependymal giant cell astrocytoma: two somatic hits of TSC2 in the tumor, without evidence of somatic mosaicism.
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.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Japan.
authors.forename: Tomotsugu
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Wakisaka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Daido
authors.forename: Soichiro
authors.initials: S
authors.lastname: Takao
authors.forename: Takashi
authors.initials: T
authors.lastname: Tamiya
authors.forename: Isao
authors.initials: I
authors.lastname: Date
authors.forename: Shoichi
authors.initials: S
authors.lastname: Koizumi
authors.forename: Yo
authors.initials: Y
authors.lastname: Niida
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008279:Magnetic Resonance Imaging; D009030:Mosaicism; D009154:Mutation / Q000235:genetics; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins