Pathogenesis of focal cortical dysplasia: possible mechanistic implification of somatic mutations
| Project/Area Number |
25640027
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKEI Nobuyuki 新潟大学, 脳研究所, 准教授 (70221372)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | てんかん / 脳神経疾患 / 皮質異形成 / 体細胞変異 / 外科病理 / 神経病理学 |
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| Outline of Final Research Achievements |
We explore the possible involvement of somatic mutations in focal cortical dysplasia (FCD) Type IIb. We performed whole exome sequencing using brain and blood samples from nine of the FCD Type IIb subjects. Somatic MTOR mutations were identified. The effect of MTOR mutations on mTOR kinase signaling was evaluated. We identified four lesion-specific somatic MTOR mutations in six of 13 (46%) individuals with FCD Type IIb showing mutant allele rates of 1.11 - 9.31%. Functional analyses showed that phosphorylation of ribosomal protein S6 in FCD Type IIb brain tissues with MTOR mutations was clearly elevated compared with control samples. Transfection of any of the four MTOR mutants into HEK293T cells led to elevated phosphorylation of 4EBP, the direct target of mTOR kinase. We found low-prevalence somatic mutations in MTOR in FCD Type IIb, indicating that activating somatic mutations in MTOR cause FCD Type IIb.
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Report
(3 results)
Research Products
(28 results)
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[Journal Article] Characteristic p57/Kip2 immunoreactivity of balloon cells in focal cortical dysplasia.2015
Author(s)
Kimura T, Kitaura H, Masuda H, Kameyama S, Saito Y, Otsuki T, Nakazawa A, Morota N, Yamamoto T, Iida K, Takahashi H, Kakita A.
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Journal Title
Neuropathology
Volume: 00
Issue: 5
Pages: 000-000
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Two siblings with cortical dysplasias: focal cortical dysplasia and hemimegalencephaly: clinicoencephalographic features.2015
Author(s)
Fukasawa T, Kubota T, Negoro T, Maruyama S, Honda R, Saito Y, Ito M, Kakita A, Sugai K, Otsuki T, Natsume J, Watanabe K.
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Journal Title
Pediatr Int
Volume: 00
Pages: 000-000
Related Report
Peer Reviewed
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[Journal Article] Electrocorticographic–Histopathologic Correlations Implying Epileptogenicity of Dysembryoplastic Neuroepithelial Tumor2013
Author(s)
Kagawa K, Iida K, Kakita A, Katagiri M, Nishimoto T, Hashizume A, Kiura Y, Hanaya R, Sugiyama K, Arihiro K, Arita K, Kurisu K
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Journal Title
Neurologia medico-chirurgica
Volume: 53
Issue: 10
Pages: 676-687
DOI
NAID
ISSN
0470-8105, 1349-8029
Related Report
Peer Reviewed
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[Presentation] Different mechanism of epileptogensis in subiculum and dentate gyrus in mesial temporal lobe epilepsy: an in vitro optical imaging study of resected human hippocampus.2014
Author(s)
Kitaura H, Shirozu H, Shimizu H, Sonoda M, Murakami H, Masuda H, Takahashi H, Kameyama S, Kakita A.
Organizer
Society for Neuroscience
Place of Presentation
Walter E. Washington Convention Center, Washington DC, USA
Year and Date
2014-11-15 – 2014-11-19
Related Report
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[Presentation] てんかん焦点の病理2014
Author(s)
柿田明美．
Organizer
第48回日本てんかん学会．
Place of Presentation
東京
Year and Date
2014-10-02 – 2014-10-03
Related Report
Invited
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[Presentation] てんかんの病理
Author(s)
柿田明美
Organizer
西新潟中央病院てんかんセンター 夏季セミナー
Place of Presentation
新潟
Related Report
Invited
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