IR@PKUHSC  > 北京大学第三临床医学院  > 肿瘤放疗科
学科主题临床医学
Genetic alteration and misexpression of Polycomb group genes in hepatocellular carcinoma
Gao, Shu-Bin1,2; Sun, Shi-Long3; Zheng, Qi-Lin1; Zhang, Li1,2; Zhu, Yuequan4; Jin, Guang-Hui1,2; Xue, Li-Xiang4
关键词Hepatocellular carcinoma Polycomb H3K27 trimetylation SNP
刊名AMERICAN JOURNAL OF CANCER RESEARCH
2015
5期:10页:2969-+
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
研究领域[WOS]Oncology
关键词[WOS]SOMATIC MUTATIONS ; DNA METHYLATION ; EZH2 ; MENIN ; TRANSCRIPTION ; REPRESSION ; MICRORNAS ; PROTEINS ; ENHANCER ; BINDING
英文摘要

Although the abnormal expression of Polycomb-group (PcG) proteins is closely associated with carcinogenesis and the clinicopathological features of hepatocellular carcinoma (HCC), the genetic mutation profile of PcG genes has not been well established. In this study of human HCC specimens, we firstly discovered a highly conserved mutation site, G553C, in the Polycomb Repressive Complex 2 (PRC2) gene enhancer of zeste homolog 2 (EZH2). This site also harbors a single nucleotide polymorphism (SNP), rs2302427, which plays an important antagonistic role in HCC. Kaplan-Meier survival curves showed that the tumor-free and overall survival of patients with EZH2 G553C were superior to those without the mutation. The G allele frequencies in patients and healthy subjects were 0.2% and 0.122%, respectively, with significant differences in distribution. The individuals carrying the GG and the GC genotypes at rs2302427 showed 3.083-fold and 1.827-fold higher risks of HCC, respectively, compared with individuals carrying the wild-type allele. Furthermore, Immunohistochemical staining revealed that the expression levels of CBX8 (in 53/123 samples) and BMI1 (in 60/130 samples) were markedly increased in human HCC specimens. Importantly, the overall and tumor-free survival rates were significantly reduced in the group of patients who simultaneously expressed PRC1 and PRC2. These results argue that a combination of PRC1 and PRC2 expression has a significant predictive/prognostic value for HCC patients. Taken together, our results indicate the abnormal expression and genetic mutation of PcG members are two independent events; cumulative genetic and epigenetic alterations act synergistically in liver carcinogenesis.

语种英语
所属项目编号81472020 ; 31071206 ; 91229111 ; 81272719
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS记录号WOS:000365990400004
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62591
专题北京大学第三临床医学院_肿瘤放疗科
作者单位1.Coll Med, Dept Basic Med Sci, Xiamen 361102, Peoples R China
2.Xiamen Univ, Fujian Prov Key Lab Chron Liver Dis & Hepatocellu, Xiamen 361102, Peoples R China
3.Jilin Univ, Minist Hlth, Key Lab Radiobiol, Changchun 130021, Peoples R China
4.Peking Univ, Hosp 3, Dept Radiat Oncol, Med Res Ctr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Gao, Shu-Bin,Sun, Shi-Long,Zheng, Qi-Lin,et al. Genetic alteration and misexpression of Polycomb group genes in hepatocellular carcinoma[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2015,5(10):2969-+.
APA Gao, Shu-Bin.,Sun, Shi-Long.,Zheng, Qi-Lin.,Zhang, Li.,Zhu, Yuequan.,...&Xue, Li-Xiang.(2015).Genetic alteration and misexpression of Polycomb group genes in hepatocellular carcinoma.AMERICAN JOURNAL OF CANCER RESEARCH,5(10),2969-+.
MLA Gao, Shu-Bin,et al."Genetic alteration and misexpression of Polycomb group genes in hepatocellular carcinoma".AMERICAN JOURNAL OF CANCER RESEARCH 5.10(2015):2969-+.
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