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Genome‐wide copy number analyses identified novel cancer genes in hepatocellular carcinoma
Author(s) -
Jia Deshui,
Wei Lin,
Guo Weijie,
Zha Ruopeng,
Bao Meiyan,
Chen Zhiao,
Zhao Yingjun,
Ge Chao,
Zhao Fangyu,
Chen Taoyang,
Yao Ming,
Li Jinjun,
Wang Hongyang,
Gu Jianren,
He Xianghuo
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24495
Subject(s) - biology , gene , carcinogenesis , hepatocellular carcinoma , copy number variation , enhancer , single nucleotide polymorphism , genetics , genome , cancer research , gene expression profiling , gene expression , genotype
Abstract A powerful way to identify driver genes with causal roles in carcinogenesis is to detect genomic regions that undergo frequent alterations in cancers. Here we identified 1,241 regions of somatic copy number alterations in 58 paired hepatocellular carcinoma (HCC) tumors and adjacent nontumor tissues using genome‐wide single nucleotide polymorphism (SNP) 6.0 arrays. Subsequently, by integrating copy number profiles with gene expression signatures derived from the same HCC patients, we identified 362 differentially expressed genes within the aberrant regions. Among these, 20 candidate genes were chosen for further functional assessments. One novel tumor suppressor (tripartite motif‐containing 35 [TRIM35]) and two putative oncogenes (hairy/enhancer‐of‐split related with YRPW motif 1 [HEY1] and small nuclear ribonucleoprotein polypeptide E [SNRPE]) were discovered by various in vitro and in vivo tumorigenicity experiments. Importantly, it was demonstrated that decreases of TRIM35 expression are a frequent event in HCC and the expression level of TRIM35 was negatively correlated with tumor size, histological grade, and serum alpha‐fetoprotein concentration. Conclusion: These results showed that integration of genomic and transcriptional data offers powerful potential for identifying novel cancer genes in HCC pathogenesis. (H EPATOLOGY 2011;) © 147.