September 22, 2019  |  

Epigenetic landscape influences the liver cancer genome architecture.

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

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.

Journal: Nature communications
DOI: 10.1038/s41467-018-03999-y
Year: 2018

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