Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma.
Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma.
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DOI：
10.1016/j.cell.2017.05.046
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发表时间：
2017-06-15
期刊：
影响因子：
64.5
通讯作者：
Cancer Genome Atlas Research Network
中科院分区：
文献类型：
--
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
肝癌是全球第二高的癌症死亡率，并且治疗选择有限。我们分析了363例肝细胞癌（HCC）病例的全外显子组测序和DNA拷贝数分析，196例HCC还分析了DNA甲基化，RNA，miRNA和蛋白质组表达。DNA测序和突变分析鉴定出显著突变的基因，包括LZTR 1、EEF 1A 1、SF 3B 1和SMARCA 4。在可能导致HCC代谢重编程的基因（ALB、APOB和CPS 1）中观察到突变或超甲基化下调的显著改变。结合五个数据平台的无监督聚类的综合分子HCC亚型确定了三种亚型，其中一种与三个HCC队列中的预后较差相关。综合分析使p53靶基因表达特征的发展与生存率低。存在抑制剂的潜在治疗靶点包括WNT信号传导、MDM 4、MET、VEGFA、MCL 1、IDH 1、TERT和免疫检查点蛋白CTLA-4、PD-1和PD-L1。人肝细胞癌患者的多重分子谱分析提供了对亚型特征的深入了解，并指出了治疗靶向的关键途径。
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. Multiplex molecular profiling of human hepatocellular carcinoma patients provides insight into subtype characteristics and points toward key pathways to target therapeutically.
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影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
DOI：
10.1093/bioinformatics/btu558
发表时间：
2014-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Chu J;Sadeghi S;Raymond A;Jackman SD;Nip KM;Mar R;Mohamadi H;Butterfield YS;Robertson AG;Birol I
通讯作者：
Birol I
影响因子：
11.2
作者：
Hoshida Y;Nijman SM;Kobayashi M;Chan JA;Brunet JP;Chiang DY;Villanueva A;Newell P;Ikeda K;Hashimoto M;Watanabe G;Gabriel S;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
3.8
作者：
Gonzalez-Angulo AM;Hennessy BT;Meric-Bernstam F;Sahin A;Liu W;Ju Z;Carey MS;Myhre S;Speers C;Deng L;Broaddus R;Lluch A;Aparicio S;Brown P;Pusztai L;Symmans WF;Alsner J;Overgaard J;Borresen-Dale AL;Hortobagyi GN;Coombes KR;Mills GB
通讯作者：
Mills GB
影响因子：
4.4
作者：
Fernandez-Banet, Julio;Lee, Nikki P.;Kan, Zhengyan
通讯作者：
Kan, Zhengyan