Gorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1
Gorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1
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DOI：
10.18632/aging.103258
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发表时间：
2020-05-31
期刊：
影响因子：
5.2
通讯作者：
Umezawa, Akihiro
中科院分区：
文献类型：
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作者：
Ikemoto, Yu;Miyashita, Toshiyuki;Umezawa, Akihiro
Gorlin综合征是一种罕见的常染色体显性遗传性疾病，以基底细胞癌和髓母细胞瘤等肿瘤发病率高。疾病特异性诱导多能干细胞（iPSC）和动物模型已被用于分析疾病的发病机制。在这项研究中，我们从四名患有Gorlin综合征（Gln-iPSCs）的患者的成纤维细胞中产生了PTCH 1基因杂合突变的iPSCs。来自四名患者的Gln-iPSC在植入免疫缺陷小鼠后100%（四分之四）的畸胎瘤发展成成髓母细胞瘤，这是Gorlin综合征的表现，但其他iPSC畸胎瘤中没有（0/584）这样做。其中一个成神经管细胞瘤显示PTCH 1基因杂合性缺失，而良性畸胎瘤，即非成神经管细胞瘤部分没有，表明Gorlin综合征患者的肿瘤发生与Gln-iPSCs之间存在密切的临床相关性。
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.