| Literature DB >> 27064257 |
Akihiro Fujimoto1, Mayuko Furuta1, Yasushi Totoki2, Tatsuhiko Tsunoda3,4,5, Mamoru Kato5,6, Yuichi Shiraishi7, Hiroko Tanaka7, Hiroaki Taniguchi1, Yoshiiku Kawakami8, Masaki Ueno9, Kunihito Gotoh10, Shun-Ichi Ariizumi11, Christopher P Wardell1, Shinya Hayami9, Toru Nakamura12, Hiroshi Aikata8, Koji Arihiro13, Keith A Boroevich3, Tetsuo Abe3, Kaoru Nakano1, Kazuhiro Maejima1, Aya Sasaki-Oku1, Ayako Ohsawa1, Tetsuo Shibuya14, Hiromi Nakamura2, Natsuko Hama2, Fumie Hosoda2, Yasuhito Arai2, Shoko Ohashi2, Tomoko Urushidate15, Genta Nagae16, Shogo Yamamoto16, Hiroki Ueda16, Kenji Tatsuno16, Hidenori Ojima17, Nobuyoshi Hiraoka18, Takuji Okusaka19, Michiaki Kubo20, Shigeru Marubashi10, Terumasa Yamada10, Satoshi Hirano12, Masakazu Yamamoto11, Hideki Ohdan21, Kazuaki Shimada22, Osamu Ishikawa10, Hiroki Yamaue9, Kazuki Chayama8,23, Satoru Miyano7,14, Hiroyuki Aburatani16, Tatsuhiro Shibata2,15, Hidewaki Nakagawa1.
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.Entities:
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Year: 2016 PMID： 27064257 DOI： 10.1038/ng.3547
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330