Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma

被引：1840

作者：

Ally, Adrian

Balasundaram, Miruna

Carlsen, Rebecca

Chuah, Eric

Clarke, Amanda

Dhalla, Noreen

Holt, Robert A.

Jones, Steven J. M.

Lee, Darlene

Ma, Yussanne

Marra, Marco A.

Mayo, Michael

Moore, Richard A.

Mungall, Andrew J.

Schein, Jacqueline E.

Sipahimalani, Payal

Tam, Angela

Thiessen, Nina

Cheung, Dorothy

Wong, Tina

Brooks, Denise

Robertson, A. Gordon

Bowlby, Reanne

Mungall, Karen

Sadeghi, Sara

Xi, Liu

Covington, Kyle

Shinbrot, Eve

Wheeler, David A.

Gibbs, Richard A.

Donehower, Lawrence A.

Wang, Linghua

Bowen, Jay

Gastier-Foster, Julie M.

Gerken, Mark

Helsel, Carmen

Leraas, Kristen M.

Lichtenberg, Tara M.

Ramirez, Nilsa C.

Wise, Lisa

Zmuda, Erik

Gabriel, Stacey B.

Meyerson, Matthew

Cibulskis, Carrie

Murray, Bradley A.

Shih, Juliann

Beroukhim, Rameen

Cherniack, Andrew D.

Schumacher, Steven E.

Saksena, Gordon

机构：

来源：

CELL | 2017年 / 169卷 / 07期

关键词：

MUTATIONAL LANDSCAPE; GENE; EXPRESSION; DNA; PREDICTION; ACCURATE; QUANTIFICATION; SIGNATURES; PHENOTYPE; DISCOVERY;

D O I：

10.1016/j.cell.2017.05.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1327 / +

页数：38

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