Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell 2017 Jun 15;169(7):1327-1341.e23
Date
06/18/2017Pubmed ID
28622513Pubmed Central ID
PMC5680778DOI
10.1016/j.cell.2017.05.046Scopus ID
2-s2.0-85020833799 (requires institutional sign-in at Scopus site) 1414 CitationsAbstract
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, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.
Author List
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu, Cancer Genome Atlas Research NetworkAuthor
Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Carcinoma, HepatocellularDNA Methylation
Genomics
Humans
Isocitrate Dehydrogenase
Liver Neoplasms
MicroRNAs
Mutation