1. Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer
- Author
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Masakazu Yamamoto, Mayuko Furuta, Satoshi Hirano, Hiroyuki Aburatani, Hiroko Tanaka, Kaoru Nakano, Hiroshi Aikata, Christopher P. Wardell, Tetsuo Shibuya, Hidenori Ojima, Nobuyoshi Hiraoka, Akihiro Fujimoto, Yuichi Shiraishi, Yasuhito Arai, Shunichi Ariizumi, Hiroaki Taniguchi, Michiaki Kubo, Terumasa Yamada, Osamu Ishikawa, Tomoko Urushidate, Aya Sasaki-Oku, Toru Nakamura, Mamoru Kato, Tatsuhiro Shibata, Yoshiiku Kawakami, Koji Arihiro, Shogo Yamamoto, Kazuki Chayama, Genta Nagae, Natsuko Hama, Keith A. Boroevich, Shigeru Marubashi, Tetsuo Abe, Shoko Ohashi, Kenji Tatsuno, Kazuhiro Maejima, Hiromi Nakamura, Kazuaki Shimada, Tatsuhiko Tsunoda, Takuji Okusaka, Yasushi Totoki, Ayako Ohsawa, Fumie Hosoda, Hideki Ohdan, Shinya Hayami, Hidewaki Nakagawa, Hiroki R. Ueda, Masaki Ueno, Kunihito Gotoh, Hiroki Yamaue, and Satoru Miyano
- Subjects
0301 basic medicine ,Genetics ,Mutation ,Point mutation ,Genomics ,Gene mutation ,Biology ,medicine.disease_cause ,Genome ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Intergenic region ,030220 oncology & carcinogenesis ,DNA Mutational Analysis ,medicine ,Gene - Abstract
Liver cancer, which is most often associated with virus infection, is prevalent worldwide, and its underlying etiology and genomic structure are heterogeneous. Here we provide a whole-genome landscape of somatic alterations in 300 liver cancers from Japanese individuals. Our comprehensive analysis identified point mutations, structural variations (STVs), and virus integrations, in noncoding and coding regions. We discovered mutational signatures related to liver carcinogenesis and recurrently mutated coding and noncoding regions, such as long intergenic noncoding RNA genes (NEAT1 and MALAT1), promoters, CTCF-binding sites, and regulatory regions. STV analysis found a significant association with replication timing and identified known (CDKN2A, CCND1, APC, and TERT) and new (ASH1L, NCOR1, and MACROD2) cancer-related genes that were recurrently affected by STVs, leading to altered expression. These results emphasize the value of whole-genome sequencing analysis in discovering cancer driver mutations and understanding comprehensive molecular profiles of liver cancer, especially with regard to STVs and noncoding mutations.
- Published
- 2016