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Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets.

ABSTRACT: 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.

SUBMITTER: Kubota Y

PROVIDER: S-EPMC7528104 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets.

Kubota Yasuo Y Seki Masafumi M Kawai Tomoko T Isobe Tomoya T Yoshida Misa M Sekiguchi Masahiro M Kimura Shunsuke S Watanabe Kentaro K Sato-Otsubo Aiko A Yoshida Kenichi K Suzuki Hiromichi H Kataoka Keisuke K Fujii Yoichi Y Shiraishi Yuichi Y Chiba Kenichi K Tanaka Hiroko H Hiwatari Mitsuteru M Oka Akira A Hayashi Yasuhide Y Miyano Satoru S Ogawa Seishi S Hata Kenichiro K Tanaka Yukichi Y Takita Junko J

Communications biology 20200930 1

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 wer ...[more]

PMID: 32999426

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Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets.

Publications

Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets.

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