Article

A case of solitary subependymal giant cell astrocytoma: Two somatic hits of TSC2 in the tumor, without evidence of somatic mosaicism

Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Japan.
Journal of Molecular Diagnostics (Impact Factor: 4.85). 10/2005; 7(4):544-9.
Source: PubMed

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.

Download full-text

Full-text

Available from: Yo Niida, Jan 19, 2016
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of multiple hamartomas in many internal organs. Mutations in either one of 2 genes, TSC1 and TSC2, have been attributed to the development of TSC. More than two-thirds of TSC patients are sporadic cases, and a wide variety of mutations in the coding region of the TSC1 and TSC2 genes have been reported. Mutational analysis of TSC1 and TSC2 genes was performed in 84 Taiwanese TSC families using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. Mutations were identified in a total of 64 (76 %) cases, including 9 TSC1 mutations (7 sporadic and 2 familial cases) and 55 TSC2 mutations (47 sporadic and 8 familial cases). Thirty-one of the 64 mutations found have not been described previously. The phenotype association is consistent with findings from other large studies, showing that disease resulting from mutations to TSC1 is less severe than disease due to TSC2 mutation. This study provides a representative picture of the distribution of mutations of the TSC1 and TSC2 genes in clinically ascertained TSC cases in the Taiwanese population. Although nearly half of the mutations identified were novel, the kinds and distribution of mutation were not different in this population compared to that seen in larger European and American studies.
    Full-text · Article · Feb 2006 · BMC Medical Genetics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical manifestations were retrospectively assessed in 5 families with tuberous sclerosis complex, including 1 pair of monozygotic twins. Interfamilial variation in tuber count was significantly larger than intrafamilial variation. Severity of epilepsy and cognitive profiles varied both between and within families, particularly between the monozygotic twins, and IQ was inversely related to tuber count. Cutaneous, renal, and cardiac findings did not appear to cluster within families. Although the monozygotic twins displayed similar physical manifestations of tuberous sclerosis complex (renal and cardiac hamartomas), they differed markedly in neurocognitive profiles. Phenotypic variation within these families may be explained largely as a function of the randomness of second-hit events that cause hamartomas in tuberous sclerosis complex or by as-yet-unidentified genetic modifiers. Familial variation in tuberous sclerosis complex phenotype has important implications for genetic counseling.
    Full-text · Article · Jan 2008 · Journal of Child Neurology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The therapy of gliomas is still challenging. This is especially true for pediatric gliomas because response to conventional cytotoxic chemotherapy agents and radiation therapy is currently often poor and because therapy-related morbidity is a significant problem in children. Stratification of tumors according to biologic characteristics and new more targeted therapies therefore hold the promise of better tumor control as well as reduced side effects. Significant progress has been made in recent years in understanding the biology of gliomas. These new insights into the molecular mechanism driving tumor growth uncover new potential molecular targets for future therapies. In addition, they start to uncover biologically defined tumor subtypes that may have to be considered independently in the search for optimal treatment regimens.
    No preview · Article · Jan 2008 · Expert Review of Anti-infective Therapy
Show more