Integrative analysis of genomic and epigenomic regulation of the transcriptome in liver cancer

Hyun Goo Woo, Ji-Hye Choi, Sarah Yoon, Byul A. Jee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh and Yoon Jun Kim ()
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Hyun Goo Woo: Ajou University School of Medicine
Ji-Hye Choi: Ajou University School of Medicine
Sarah Yoon: Ajou University School of Medicine
Byul A. Jee: Ajou University School of Medicine
Eun Ju Cho: Seoul National University College of Medicine
Jeong-Hoon Lee: Seoul National University College of Medicine
Su Jong Yu: Seoul National University College of Medicine
Jung-Hwan Yoon: Seoul National University College of Medicine
Nam-Joon Yi: Seoul National University College of Medicine
Kwang-Woong Lee: Seoul National University College of Medicine
Kyung-Suk Suh: Seoul National University College of Medicine
Yoon Jun Kim: Seoul National University College of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Hepatocellular carcinoma harbors numerous genomic and epigenomic aberrations of DNA copy numbers and DNA methylation. Transcriptomic deregulation by these aberrations plays key driver roles in heterogeneous progression of cancers. Here, we profile DNA copy numbers, DNA methylation, and messenger RNA expression levels from 64 cases of hepatocellular carcinoma specimens. We find that the frequencies of the aberrancies of the DNA copy-number-correlated (CNVcor) expression genes and the methylation-correlated expression (METcor) genes are co-regulated significantly. Multi-omics integration of the CNVcor and METcor genes reveal three prognostic subtypes of hepatocellular carcinoma, which can be validated by an independent data. The most aggressive subtype expressing stemness genes has frequent BAP1 mutations, implying its pivotal role in the aggressive tumor progression. In conclusion, our integrative analysis of genomic and epigenomic regulation provides new insights on the multi-layered pathobiology of hepatocellular carcinoma, which might be helpful in developing precision management for hepatocellular carcinoma patients.

Date: 2017
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DOI: 10.1038/s41467-017-00991-w

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