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      Necroptosis microenvironment directs lineage commitment in liver cancer

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          Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma.

          Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integration of genomics, transcriptomics, and metabolomics. While ICC and HCC share recurrently mutated genes, including TP53, ARID1A, and ARID2, mitotic checkpoint anomalies distinguish the C1 subtype with key drivers PLK1 and ECT2, whereas the C2 subtype is linked to obesity, T cell infiltration, and bile acid metabolism. These molecular subtypes are found in 582 Asian, but less so in 265 Caucasian patients. Thus, Asian ICC and HCC, while clinically treated as separate entities, share common molecular subtypes with similar actionable drivers to improve precision therapy.
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            Functional and genetic deconstruction of the cellular origin in liver cancer.

            During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution of the disrupted hepatic microenvironment to liver carcinogenesis.
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              Using MACS to identify peaks from ChIP-Seq data.

              Model-based Analysis of ChIP-Seq (MACS) is a command-line tool designed by X. Shirley Liu and colleagues to analyze data generated by ChIP-Seq experiments in eukaryotes, especially mammals. MACS can be used to identify transcription factor binding sites and histone modification-enriched regions if the ChIP-Seq data, with or without control samples, are given. This unit describes two basic protocols that provide detailed information on how to use MACS to identify either the binding sites of a transcription factor or the enriched regions of a histone modification with broad peaks. Furthermore, the basic ideas for the MACS algorithm and its appropriate usage are discussed.
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                Author and article information

                Journal
                Nature
                Nature
                Springer Nature America, Inc
                0028-0836
                1476-4687
                September 12 2018
                Article
                10.1038/s41586-018-0519-y
                30209397
                b90ca0aa-93a6-4bda-af0b-568fb495bb5d
                © 2018

                http://www.springer.com/tdm

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