Trans-ancestry mutational landscape of hepatocellular carcinoma genomes
書誌事項
- 公開日
- 2014-11-02
- 資源種別
- journal article
- 権利情報
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- http://www.springer.com/tdm
- DOI
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- 10.1038/ng.3126
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
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.
収録刊行物
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- Nature Genetics
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Nature Genetics 46 (12), 1267-1273, 2014-11-02
Springer Science and Business Media LLC
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キーワード
- Hepatitis B virus
- Principal Component Analysis
- Carcinoma, Hepatocellular
- Models, Statistical
- Genome, Human
- TOR Serine-Threonine Kinases
- DNA Mutational Analysis
- Liver Neoplasms
- Genome, Viral
- Hepacivirus
- United States
- Gene Expression Regulation, Neoplastic
- Asian People
- Japan
- Mutation
- Humans
- CpG Islands
- Exome
- Telomerase
- Algorithms
詳細情報 詳細情報について
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- CRID
- 1360002216806443648
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- DOI
- 10.1038/ng.3126
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- ISSN
- 15461718
- 10614036
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- PubMed
- 25362482
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE