Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets.
Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets.
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儿科生殖细胞肿瘤的综合遗传分析确定了潜在的药物靶点。
DOI：
10.1038/s42003-020-01267-8
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发表时间：
2020-09-30
影响因子：
5.9
通讯作者：
Takita J
中科院分区：
文献类型：
--
作者：
Kubota Y;Seki M;Kawai T;Isobe T;Yoshida M;Sekiguchi M;Kimura S;Watanabe K;Sato-Otsubo A;Yoshida K;Suzuki H;Kataoka K;Fujii Y;Shiraishi Y;Chiba K;Tanaka H;Hiwatari M;Oka A;Hayashi Y;Miyano S;Ogawa S;Hata K;Tanaka Y;Takita J
为了阐明小儿生殖细胞肿瘤（GCT）的分子发病机制，我们对51例GCT样本进行了DNA甲基化阵列分析、全转录组测序、靶向捕获测序和单核苷酸多态性阵列分析其中生殖细胞瘤6例，胚胎癌2例，未成熟畸胎瘤4例，成熟畸胎瘤3例，卵黄囊瘤30例，混合性生殖细胞肿瘤6例。在51份样本中，11份来自婴儿，23份来自幼儿，17份来自≥10岁。51个样本中有16个在性腺外区域发育。生殖细胞瘤显示多能基因上调和整体低甲基化。多能基因在胚胎癌中也有高表达。这些基因可能在胚胎癌中发挥重要作用，因为它们的结合位点是低甲基化的。卵黄囊肿瘤表现出过度表达的内胚层基因，如GATA 6和FOXA 2，其结合位点是低甲基化的。有趣的是，婴儿卵黄囊肿瘤的DNA甲基化模式与在年龄较大的儿童中观察到的不同。畸胎瘤有较高的外胚层基因表达，提示三胚层的性质。基于我们的研究结果，我们认为KIT，TNFRSF8和ERBB4可能是合适的目标，分别用于治疗生殖细胞瘤，胚胎癌和卵黄囊肿瘤。Yasuo Kubota等人报告了对51例年龄从2个月到19岁的儿童生殖细胞肿瘤患者的多组学分析。他们确定了每种主要亚型的独特甲基化，表达和突变模式，并提出了针对三种主要亚型治疗的潜在靶基因。
To elucidate the molecular pathogenesis of pediatric germ cell tumors (GCTs), we performed DNA methylation array analysis, whole transcriptome sequencing, targeted capture sequencing, and single-nucleotide polymorphism array analysis using 51 GCT samples (25 female, 26 male), including 6 germinomas, 2 embryonal carcinomas, 4 immature teratomas, 3 mature teratomas, 30 yolk sac tumors, and 6 mixed germ cell tumors. Among the 51 samples, 11 were from infants, 23 were from young children, and 17 were from those aged ≥10 years. Sixteen of the 51 samples developed in the extragonadal regions. Germinomas showed upregulation of pluripotent genes and global hypomethylation. Pluripotent genes were also highly expressed in embryonal carcinomas. These genes may play essential roles in embryonal carcinomas given that their binding sites are hypomethylated. Yolk sac tumors exhibited overexpression of endodermal genes, such as GATA6 and FOXA2, the binding sites of which were hypomethylated. Interestingly, infant yolk sac tumors had different DNA methylation patterns from those observed in older children. Teratomas had higher expression of ectodermal genes, suggesting a tridermal nature. Based on our results, we suggest that KIT, TNFRSF8, and ERBB4 may be suitable targets for the treatment of germinoma, embryonal carcinomas, and yolk sac tumors, respectively. Yasuo Kubota et al. report a multi-omic analysis of pediatric germ cell tumors from 51 patients ranging in age from 2 months to 19 years. They identify unique methylation, expression, and mutational patterns for each of the main subtypes and propose potential target genes for treatments against the three main subtypes.
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影响因子：
16.6
作者：
Litchfield, Kevin;Summersgill, Brenda;Yost, Shawn;Sultana, Razvan;Labreche, Karim;Dudakia, Darshna;Renwick, Anthony;Seal, Sheila;Al-Saadi, Reem;Broderick, Peter;Turner, Nicholas C.;Houlston, Richard S.;Huddart, Robert;Shipley, Janet;Turnbull, Clare
通讯作者：
Turnbull, Clare
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通讯作者：
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12.7
作者：
Fukushima, Shintaro;Otsuka, Ayaka;Ichimura, Koichi
通讯作者：
Ichimura, Koichi
影响因子：
2.9
作者：
Huang, Xiang;Zhang, Rong;Zhou, Liang-Fu
通讯作者：
Zhou, Liang-Fu
人类原始生殖细胞的转录组和 DNA 甲基化组景观
影响因子：
64.5
作者：
Guo, Fan;Yan, Liying;Qiao, Jie
通讯作者：
Qiao, Jie