2019 Fiscal Year Final Research Report
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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| Keywords | 母斑基底細胞癌症候群 / iPS細胞 / CRISPR/Cas9 |
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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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| Free Research Field |
分子遺伝学
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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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