Open AccessGorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1
Author(s) -
Yu Ikemoto,
Toshiyuki Miyashita,
Michiyo Nasu,
Hiromi Hatsuse,
Kazuhiro Kajiwara,
Kiyotaka Fujii,
Toshino Motojima,
Ibuki Kokido,
Masashi Toyoda,
Akihiro Umezawa
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.103258
Subject(s) - ptch1 , loss of heterozygosity , medulloblastoma , induced pluripotent stem cell , biology , genetics , microbiology and biotechnology , hedgehog , gene , embryonic stem cell , allele
Gorlin syndrome is a rare autosomal dominant hereditary disease with a high incidence of tumors such as basal cell carcinoma and medulloblastoma. Disease-specific induced pluripotent stem cells (iPSCs) and an animal model have been used to analyze disease pathogenesis. In this study, we generated iPSCs derived from fibroblasts of four patients with Gorlin syndrome (Gln-iPSCs) with heterozygous mutations of the PTCH1 gene. Gln-iPSCs from the four patients developed into medulloblastoma, a manifestation of Gorlin syndrome, in 100% (four out of four), of teratomas after implantation into immunodeficient mice, but none (0/584) of the other iPSC-teratomas did so. One of the medulloblastomas showed loss of heterozygosity in the PTCH1 gene while the benign teratoma, i.e. the non-medulloblastoma portion, did not, indicating a close clinical correlation between tumorigenesis in Gorlin syndrome patients and Gln-iPSCs.