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bioRxiv · 10.1101/858555

Gorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1

Ikemoto, Y.·Miyashita, T.·Nasu, M.·Hatsuse, H.·Kajiwara, K.·Fujii, K.·Motojima, T.·Toyoda, M.·UMEZAWA, A.
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Abstract

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.

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Ikemoto, Y., Miyashita, T., Nasu, M., Hatsuse, H., Kajiwara, K., Fujii, K., Motojima, T., Toyoda, M., UMEZAWA, A.. 2019-11-29. Gorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1. https://doi.org/10.1101/858555

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