Investigation of molecular pathogenesis of nevoid basal cell carcinoma syndrome using disease-specific and gene-edited iPSCs
| Project/Area Number |
17K10061
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 母斑基底細胞癌症候群 / iPS細胞 / CRISPR/Cas9 / Gorlin症候群 / PTCH1 / 髄芽腫 / CRISPR/Cas9システム / CRISPR/Cas9 システム / 遺伝子 / 遺伝学 / 再生医学 / 癌 |
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| Outline of Final Research Achievements |
Induced pluripotent stem cells (iPSCs) have been established from nevoid basal cell carcinoma syndrome (NBCCS) patients (PTCH1+/- iPSCs). Teratomas that developed from these iPSCs contained medulloblastoma tissues. Interestingly, these medulloblastomas carried second hit mutations in the normal allele of the PTCH1 gene.
Furthermore, using CRISPR/Cas9 system, we established iPSCs carrying mutations in both alleles of PTCH1 (PTCH1-/- iPSCs). Teratomas that developed from PTCH1-/- iPSCs mostly consisted of ectoderm tissues including medulloblastoma. Endoderm and mesoderm tissues were rarely observed, indicating that PTCH1-/- iPSCs have a strong tendency to differentiate into ectoderm cells.
These results are expected to contribute to the understanding the molecular mechanism of tumor formation in NBCCS patients and screening candidate drugs for the treatment of these tumors.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、母斑基底細胞癌症候群（NBCCS）に発症する髄芽腫の新たな実験モデルがヒト細胞を用いて確立されたと考えられる。今後iPS細胞をある程度分化させた後でマウスの移植することで、基底細胞癌など、髄芽腫以外の腫瘍の発症モデルの確立も期待される。
また本モデルは将来NBCCSに発症する腫瘍に有効な薬剤のスクリーニングにも応用可能と思われる。
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] A novel PTCH1 mutation in basal cell nevus syndrome with rare craniofacial features2019
Author(s)
Murata Y, Kurosaka H, Ohata Y, Aikawa T, Takahata S, Fujii K, Miyashita T, Morita C, Inubushi T, Kubota T, Sakai N, Ozono K, Kogo M, Yamashiro T.
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Journal Title
Human Genome Variation
Volume: 6
Issue: 1
Pages: 16-16
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] L-leucine and SPNS1 coordinately ameliorate dysfunction of autophagy in mouse and human Niemann-Pick type C disease.2017
Author(s)
Yanagisawa H, Ishii T, Endo K, Kawakami E, Nagao K, Miyashita T, Akiyama K, Watabe K, Komatsu M, Yamamoto D, Eto Y.
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Journal Title
Sci Rep
Volume: 7
Issue: 1
Pages: 15994-15994
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Somatic mosaicism containing double mutations in PTCH1 revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome.2017
Author(s)
Ikemoto, Y., Takayama, Y., Fujii, K., Masuda, M., Kato, C., Hatsuse, H., Fujitani, K., Nagao, K., Kameyama, K., Ikehara, H., Toyoda, M., Umezawa, A. and Miyashita, T.
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Journal Title
Journal of Medical Genetics
Volume: －
Issue: 8
Pages: 579-584
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Brain morphology in children with nevoid basal cell carcinoma syndrome.2017
Author(s)
Shiohama, T., Fuji, K., Miyashita, T., Mizuochi, H., Uchikawa, H., Shimojo, N.
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Journal Title
American Journal of Medical Genetics A
Volume: 173
Issue: 4
Pages: 946-952
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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