Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity

• DOI: 10.1038/ncomms7120
• Publication Date: 2015-01-30T13:49:11Z
• Authors: Akihiro Fujimoto; Mayuko Furuta; Yuichi Shiraishi; Kunihito Gotoh; Yoshiiku Kawakami; Koji Arihiro; Toru Nakamura; Masaki Ueno; Shun-ichi Ariizumi; Ha Hai Nguyen; Daichi Shigemizu; Tetsuo Abe; Keith A. Boroevich; Kaoru Nakano; Aya Sasaki; Rina Kitada; Kazihiro Maejima; Yujiro Yamamoto; Hiroko Tanaka; Tetsuo Shibuya; Tatsuhiro Shibata; Hidenori Ojima; Kazuaki Shimada; Shinya Hayami; Yoshinobu Shigekawa; Hiroshi Aikata; Hideki Ohdan; Shigeru Marubashi; Terumasa Yamada; Michiaki Kubo; Satoshi Hirano; Osamu Ishikawa; Masakazu Yamamoto; Hiroki Yamaue; Kazuaki Chayama; Satoru Miyano; Tatsuhiko Tsunoda; Hidewaki Nakagawa
• Keywords: Liver Cancer; Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma and combined hepatocellular show varying degrees of biliary epithelial differentiation, which can be defined as liver cancer displaying phenotype (LCB). LCB is second in the incidence for cancers with without chronic hepatitis background more aggressive than carcinoma (HCC). To gain insight into its molecular alterations, we performed whole-genome sequencing analysis on 30 LCBs. Here show, genome-wide substitution patterns LCBs developed livers overlapped those 60 HCCs, whereas hepatitis-negative diverged. The subsequent validation study 68 identified recurrent mutations TERT promoter, chromatin regulators (BAP1, PBRM1 ARID2), a synapse organization gene (PCLO), IDH genes KRAS. frequencies KRAS IDHs mutations, are associated poor disease-free survival, were significantly higher This reveals strong impact mutational landscape genetic diversity among phenotypes cancers. Fujimoto et al. characterize profile identify IDHassociated survival.