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Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets.
Kubota, Yasuo; Seki, Masafumi; Kawai, Tomoko; Isobe, Tomoya; Yoshida, Misa; Sekiguchi, Masahiro; Kimura, Shunsuke; Watanabe, Kentaro; Sato-Otsubo, Aiko; Yoshida, Kenichi; Suzuki, Hiromichi; Kataoka, Keisuke; Fujii, Yoichi; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Hiwatari, Mitsuteru; Oka, Akira; Hayashi, Yasuhide; Miyano, Satoru; Ogawa, Seishi; Hata, Kenichiro; Tanaka, Yukichi; Takita, Junko.
Affiliation
  • Kubota Y; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Seki M; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Kawai T; Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
  • Isobe T; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Yoshida M; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Sekiguchi M; Clinical Research Institute and Department of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
  • Kimura S; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Watanabe K; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Sato-Otsubo A; Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
  • Yoshida K; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Suzuki H; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Kataoka K; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Fujii Y; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Shiraishi Y; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Chiba K; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Tanaka H; Section of Genome Analysis Platform, Center for Cancer Genomic and Advanced Therapeutics, National Cancer Center, Tokyo, Japan.
  • Hiwatari M; Section of Genome Analysis Platform, Center for Cancer Genomic and Advanced Therapeutics, National Cancer Center, Tokyo, Japan.
  • Oka A; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Hayashi Y; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Miyano S; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan.
  • Ogawa S; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Hata K; Institute of Physiology and Medicine, Jobu University, Takasaki, Japan.
  • Tanaka Y; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Takita J; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Commun Biol ; 3(1): 544, 2020 09 30.
Article in En | MEDLINE | ID: mdl-32999426
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.
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Full text: 1 Database: MEDLINE Main subject: Neoplasms, Germ Cell and Embryonal Limits: Child / Child, preschool / Female / Humans / Infant / Male Language: En Journal: Commun Biol Year: 2020 Type: Article Affiliation country: Japan
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Full text: 1 Database: MEDLINE Main subject: Neoplasms, Germ Cell and Embryonal Limits: Child / Child, preschool / Female / Humans / Infant / Male Language: En Journal: Commun Biol Year: 2020 Type: Article Affiliation country: Japan