TY - JOUR
T1 - Epigenetic landscape influences the liver cancer genome architecture
AU - Hama, Natsuko
AU - Totoki, Yasushi
AU - Miura, Fumihito
AU - Tatsuno, Kenji
AU - Saito-Adachi, Mihoko
AU - Nakamura, Hiromi
AU - Arai, Yasuhito
AU - Hosoda, Fumie
AU - Urushidate, Tomoko
AU - Ohashi, Shoko
AU - Mukai, Wakako
AU - Hiraoka, Nobuyoshi
AU - Aburatani, Hiroyuki
AU - Ito, Takashi
AU - Shibata, Tatsuhiro
N1 - Funding Information:
The supercomputing resource ‘SHIROKANE’ was provided by the Human Genome Center at The University of Tokyo. This work was supported in part by the Practical Research for Innovative Cancer Control and Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from the Japan Agency for Medical Research and Development (AMED), National Cancer Center Research and Development Funds (26-A-5), and CREST from the Japan Science and Technology Agency; the National Cancer Center Biobank is supported by the National Cancer Center Research and Development Fund, Japan.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-03999-y
DO - 10.1038/s41467-018-03999-y
M3 - Article
C2 - 29691395
AN - SCOPUS:85045896098
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1643
ER -
