New classification of cancers based on transposon expression patterns: A trial in neuroblastoma stages 4 and 4S

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  • Yamada Shiro
    Department of Pediatrics, Oiso Hospital, Tokai University
  • Ito Jumpei
    Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo
  • Hayano Takahide
    Department of Systems Bioinformatics, Graduate School of Medicine, Yamaguchi University
  • Nakaoka Hirofumi
    Human Genetics Laboratory, National Institute of Genetics
  • Kimura Tetsuaki
    Human Genetics Laboratory, National Institute of Genetics
  • Sugimoto Ryota
    Human Genetics Laboratory, National Institute of Genetics
  • Mochizuki Hiroyuki
    Department of Pediatrics, Tokai University School of Medicine
  • Inoue Ituro
    Human Genetics Laboratory, National Institute of Genetics

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Other Title
  • トランスポゾンによる悪性腫瘍の新しい分類の可能性
  • ～神経芽腫ステージ4Sに着目して～

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<p>Transposable elements (TEs) are “DNA parasites” of the genome, which transpose, proliferate and comprise about 45% of the human genome. The transposition of TEs may harm the genome with the destruction of genes, thereby causing diseases. However, TEs have transcription factor binding sites (TFBSs), and a substantial fraction of them act as enhancers for nearby genes. Thus, TEs are required for genome functions. The adaptational capability of the genome is supported by the flexible use of TFBSs derived from TEs, called “exaptation”. Given that active enhancers are transcribed to RNA, transcribed TEs may reflect part of the “enhancer landscape” of cells. Neuroblastomas (NBs) have a unique stage called 4S in which they regress spontaneously even if stage 4 (st4) shows poor prognosis. A comparison study of st4 and 4S may provide the keys to finding the causes underlying the malignant characteristics of NBs and also the benign behavior of 4S. NBs show a relatively low frequency of gene mutations, so the amount of information obtained by studying NBs is limited. We introduced a method of TE transcriptome analysis, which may show another aspect of genome dysfunctions in TE-derived enhancer systems. Both gene and TE expression data have the power to cluster st4 and 4S clearly. They also brought about subclusters of st4, which show different survival courses. The significance of TE-based NB clusters will be revealed and would open a new age of medical discoveries.</p>

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