Gorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1
| Autor: | Michiyo Nasu, Toshiyuki Miyashita, Katsunori Fujii, Hiromi Hatsuse, Masashi Toyoda, Yu Ikemoto, Toshino Motojima, Akihiro Umezawa, Kazuhiro Kajiwara |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male endocrine system Aging PTCH1 Adolescent induced pluripotent stem cells Loss of Heterozygosity Disease medulloblastoma medicine.disease_cause Loss of heterozygosity Animal model heterozygosity Humans Medicine Basal cell carcinoma Cerebellar Neoplasms Child Induced pluripotent stem cell neoplasms Medulloblastoma business.industry Basal Cell Nevus Syndrome Cell Biology PTCH1 Gene medicine.disease Gorlin syndrome Patched-1 Receptor stomatognathic diseases Cancer research Female business Carcinogenesis Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Gorlin syndrome is a rare autosomal dominant hereditary disease with high incidence of tumors such as basal cell carcinoma and medulloblastoma. Disease-specific induced pluripotent stem cells (iPSCs) have now been used as a model to analyze disease pathogenesis as well as an animal model. In this study, we generated iPSCs derived from fibroblasts of four patients with Gorlin syndrome (Gln-iPSCs) with a heterozygous mutation of the PTCH1 gene. Gln-iPSCs from the four patients developed medulloblastoma in 100% (four out of four), a manifestation of Gorlin syndrome, in the teratomas after implantation into immunodeficient mice, but none (0/584) of the other iPSC-teratomas. One of the medulloblastomas had loss of heterozygosity in the PTCH1 gene while benign teratoma, i.e. non-medulloblastoma part, did not, indicating a close clinical correlation between tumorigenesis in Gorlin syndrome patients and Gln-iPSCs. |
| Databáze: | OpenAIRE |
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