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Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma

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Author(s)
The Cancer Genome Atlas Research Network
Keimyung Author(s)
Kang, Koo JeongAhn, Keun Soo
Department
Dept. of Surgery (외과학)
Journal Title
Cell
Issued Date
2017
Volume
169
Issue
7
Keyword
expression profilehepatocellular carcinomametabolic reprogrammingpromoter hypermethylationsignificantly mutated genessonic hedgehog signalingstem cell phenotypecancer subtypingIDH1/2TP53
Abstract
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 we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation 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,M4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.
Keimyung Author(s)(Kor)
안근수
강구정
Publisher
School of Medicine
Citation
The Cancer Genome Atlas Research Network. (2017). Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell, 169(7), 1327–1327, e23. doi: 10.1016/j.cell.2017.05.046
Type
Article
ISSN
0092-8674
DOI
10.1016/j.cell.2017.05.046
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32383
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
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