| Literature DB >> 25636086 |
Akihiro Fujimoto1, Mayuko Furuta2, Yuichi Shiraishi3, Kunihito Gotoh4, Yoshiiku Kawakami5, Koji Arihiro6, Toru Nakamura7, Masaki Ueno8, Shun-ichi Ariizumi9, Ha Hai Nguyen10, Daichi Shigemizu11, Tetsuo Abe11, Keith A Boroevich11, Kaoru Nakano2, Aya Sasaki2, Rina Kitada2, Kazihiro Maejima2, Yujiro Yamamoto2, Hiroko Tanaka12, Tetsuo Shibuya12, Tatsuhiro Shibata13, Hidenori Ojima14, Kazuaki Shimada15, Shinya Hayami8, Yoshinobu Shigekawa8, Hiroshi Aikata5, Hideki Ohdan16, Shigeru Marubashi4, Terumasa Yamada4, Michiaki Kubo17, Satoshi Hirano7, Osamu Ishikawa4, Masakazu Yamamoto9, Hiroki Yamaue8, Kazuaki Chayama18, Satoru Miyano19, Tatsuhiko Tsunoda11, Hidewaki Nakagawa2.
Abstract
Intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma show varying degrees of biliary epithelial differentiation, which can be defined as liver cancer displaying biliary phenotype (LCB). LCB is second in the incidence for liver cancers with and without chronic hepatitis background and more aggressive than hepatocellular carcinoma (HCC). To gain insight into its molecular alterations, we performed whole-genome sequencing analysis on 30 LCBs. Here we show, the genome-wide substitution patterns of LCBs developed in chronic hepatitis livers overlapped with those of 60 HCCs, whereas those of hepatitis-negative LCBs diverged. The subsequent validation study on 68 LCBs identified recurrent mutations in TERT promoter, chromatin regulators (BAP1, PBRM1 and ARID2), a synapse organization gene (PCLO), IDH genes and KRAS. The frequencies of KRAS and IDHs mutations, which are associated with poor disease-free survival, were significantly higher in hepatitis-negative LCBs. This study reveals the strong impact of chronic hepatitis on the mutational landscape in liver cancer and the genetic diversity among LCBs.Entities:
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Year: 2015 PMID： 25636086 DOI： 10.1038/ncomms7120
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919