Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma

By Adrian Ally, M. Balasundaram, R. Carlsen, E. Chuah, A. Clarke, Noreen Dhalla, R. Holt, Steven J. M. Jones, Darlene Lee, Yussanne Ma and 226 more. Cell, 2017

2,216 citations recorded by the source corpus.

SUMMARY Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole exome sequencing and DNA copy number analyses, and 196 HCC also by DNA methylation, RNA, miRNA, and proteomic expression. DNA sequencing and mutation analysis identified significantly mutated genes including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or down-regulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/68ed536d2e9027925376b6523ebc50fc00771e86

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In Cancer Research

1. Peter W. Laird
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1. Katherine A. Hoadley
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4. Ronglai Shen
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Citations in the corpus

• Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer (2018, background): “…of stemness, attesting to their underlying molecular heterogeneity, as previously reported (Cancer Genome Atlas Network, 2015; Cancer Genome Atlas Research Network, 2011, 2012, 2014a, 2014b, 2015a, 2015b, 2017; Cancer Genome Atlas Research Network et al., 2013a, 2013b; Robertson et al., 2017).”