Epigenetic landscape influences the liver cancer genome architecture

Natsuko Hama, Yasushi Totoki, Fumihito Miura, Kenji Tatsuno, Mihoko Saito-Adachi, Hiromi Nakamura, Yasuhito Arai, Fumie Hosoda, Tomoko Urushidate, Shoko Ohashi, Wakako Mukai, Nobuyoshi Hiraoka, Hiroyuki Aburatani, Takashi Ito, Tatsuhiro Shibata

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8 Citations (Scopus)

Abstract

The accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome. Individual mutation signatures depend on chromatin status, especially, signatures with a higher transcriptional strand bias occur within active chromatic areas. Hepatitis B virus (HBV) integration sites are frequently detected within inactive chromatin regions in cancer cells, as a consequence of negative selection for integrations in active chromatin regions. Ultra-high structural instability and preserved unmethylation of integrated HBV genomes are observed. We conclude that both precancerous and somatic epigenetic features contribute to the cancer genome architecture.

Original languageEnglish
Article number1643
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Hama, N., Totoki, Y., Miura, F., Tatsuno, K., Saito-Adachi, M., Nakamura, H., Arai, Y., Hosoda, F., Urushidate, T., Ohashi, S., Mukai, W., Hiraoka, N., Aburatani, H., Ito, T., & Shibata, T. (2018). Epigenetic landscape influences the liver cancer genome architecture. Nature communications, 9(1), [1643]. https://doi.org/10.1038/s41467-018-03999-y