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A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors

Author

Listed:
  • Kyuto Sonehara

    (Osaka University Graduate School of Medicine
    Osaka University)

  • Yui Kimura

    (National Center for Child Health and Development
    National Cancer Center Research Institute)

  • Yoshiko Nakano

    (National Cancer Center Research Institute
    The University of Tokyo Hospital)

  • Tatsuya Ozawa

    (National Cancer Center Research Institute)

  • Meiko Takahashi

    (Kyoto University Graduate School of Medicine)

  • Ken Suzuki

    (Osaka University Graduate School of Medicine)

  • Takashi Fujii

    (National Defense Medical College
    Juntendo University School of Medicine
    Juntendo University)

  • Yuko Matsushita

    (Juntendo University School of Medicine
    Juntendo University)

  • Arata Tomiyama

    (National Defense Medical College
    Juntendo University School of Medicine
    Juntendo University)

  • Toshihiro Kishikawa

    (Osaka University Graduate School of Medicine
    Osaka University Graduate School of Medicine
    Aichi Cancer Center Hospital)

  • Kenichi Yamamoto

    (Osaka University Graduate School of Medicine
    Osaka University Graduate School of Medicine
    Osaka University)

  • Tatsuhiko Naito

    (Osaka University Graduate School of Medicine
    the University of Tokyo)

  • Tomonari Suzuki

    (Saitama Medical University International Medical Center)

  • Shigeru Yamaguchi

    (Hokkaido University)

  • Tomoru Miwa

    (Keio University School of Medicine)

  • Hikaru Sasaki

    (Keio University School of Medicine)

  • Masashi Kitagawa

    (Shizuoka Children’s Hospital)

  • Naoyuki Ohe

    (Gifu University)

  • Junya Fukai

    (Wakayama Medical University School of Medicine)

  • Hideki Ogiwara

    (National Center for Child Health and Development)

  • Atsufumi Kawamura

    (Hyogo Prefectural Kobe Children’s Hospital)

  • Satoru Miyawaki

    (the University of Tokyo)

  • Fumihiko Matsuda

    (Kyoto University Graduate School of Medicine)

  • Nobutaka Kiyokawa

    (National Center for Child Health and Development)

  • Koichi Ichimura

    (National Cancer Center Research Institute
    Juntendo University)

  • Ryo Nishikawa

    (Saitama Medical University International Medical Center)

  • Yukinori Okada

    (Osaka University Graduate School of Medicine
    Osaka University
    Osaka University
    Osaka University)

  • Keita Terashima

    (National Center for Child Health and Development)

Abstract

Intracranial germ cell tumors (IGCTs) are rare brain neoplasms that mainly occur in children and adolescents with a particularly high incidence in East Asian populations. Here, we conduct a genome-wide association study (GWAS) of 133 patients with IGCTs and 762 controls of Japanese ancestry. A common 4-bp deletion polymorphism in an enhancer adjacent to BAK1 is significantly associated with the disease risk (rs3831846; P = 2.4 × 10−9, odds ratio = 2.46 [95% CI: 1.83–3.31], minor allele frequency = 0.43). Rs3831846 is in strong linkage disequilibrium with a testicular GCTs susceptibility variant rs210138. In-vitro reporter assays reveal rs3831846 to be a functional variant attenuating the enhancer activity, suggesting its contribution to IGCTs predisposition through altering BAK1 expression. Risk alleles of testicular GCTs derived from the European GWAS show significant positive correlations in the effect sizes with the Japanese IGCTs GWAS (P = 1.3 × 10−4, Spearman’s ρ = 0.48). These results suggest the shared genetic susceptibility of GCTs beyond ethnicity and primary sites.

Suggested Citation

  • Kyuto Sonehara & Yui Kimura & Yoshiko Nakano & Tatsuya Ozawa & Meiko Takahashi & Ken Suzuki & Takashi Fujii & Yuko Matsushita & Arata Tomiyama & Toshihiro Kishikawa & Kenichi Yamamoto & Tatsuhiko Nait, 2022. "A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32005-9
    DOI: 10.1038/s41467-022-32005-9
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    1. Kyuto Sonehara & Yoshitaka Yano & Tatsuhiko Naito & Shinobu Goto & Hiroyuki Yoshihara & Takahiro Otani & Fumiko Ozawa & Tamao Kitaori & Koichi Matsuda & Takashi Nishiyama & Yukinori Okada & Mayumi Sug, 2024. "Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss," Nature Communications, Nature, vol. 15(1), pages 1-9, December.

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