Trans-ancestry mutational landscape of hepatocellular carcinoma genomes
| Autor: | Genta Nagae, Norihiro Kokudo, Harsha Doddapaneni, Tomoko Urushidate, Fumie Hosoda, Eve Shinbrot, Hiromi Nakamura, Chad J. Creighton, David A. Wheeler, Shumpei Ishikawa, Hidenori Ojima, Yasuhito Arai, John A. Goss, Kim Walker, Natsuko Hama, Yutaka Midorikawa, Kengo Gotoh, Jacfranz J. Guiteau, Shingo Tsuji, Tomoo Kosuge, Megan Lehmkuhl, Akimasa Hayashi, Mariko Tanaka, Shogo Yamamoto, Naoko Okada, Ronald T. Cotton, Yiming Zhu, Tatsuhiro Shibata, Kazuaki Shimada, Mamoru Kato, Hiroyuki Aburatani, Shoko Ohashi, Huyen Dinh, Richard A. Gibbs, Kenji Tatsuno, Masashi Fukayama, Junji Shibahara, Lawrence A. Donehower, Tadatoshi Takayama, Donna M. Muzny, Min Wang, Hiroki R. Ueda, Marie-Claude Gingras, Yasushi Totoki, Kyle R. Covington, Mahmoud Dahdouli, Takuji Okusaka, Betty L. Slagle |
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| Rok vydání: | 2013 |
| Předmět: |
Hepatitis B virus
Carcinoma Hepatocellular DNA Mutational Analysis Genome Viral Hepacivirus Biology Genome White People Asian People Japan Genetics medicine Humans Exome Gene Telomerase PI3K/AKT/mTOR pathway Principal Component Analysis Models Statistical Genome Human TOR Serine-Threonine Kinases Liver Neoplasms medicine.disease United States Chromatin Gene Expression Regulation Neoplastic CpG site Mutation CpG Islands Liver cancer Algorithms |
| Zdroj: | Nature genetics. 46(12) |
| ISSN: | 1546-1718 |
| Popis: | Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different populations uncovered 30 candidate driver genes and 11 core pathway modules. Furthermore, a collaboration of two large-scale cancer genome projects comparatively analyzed the trans-ancestry substitution signatures in 608 liver cancer cases and identified unique mutational signatures that predominantly contribute to Asian cases. This work elucidates previously unexplored ancestry-associated mutational processes in HCC development. A combination of hotspot TERT promoter mutation, TERT focal amplification and viral genome integration occurs in more than 68% of cases, implicating TERT as a central and ancestry-independent node of hepatocarcinogenesis. Newly identified alterations in genes encoding metabolic enzymes, chromatin remodelers and a high proportion of mTOR pathway activations offer potential therapeutic and diagnostic opportunities. |
| Databáze: | OpenAIRE |
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