Genome-wide copy number analyses identified novel cancer genes in hepatocellular carcinoma.

Abstract

UNLABELLED:

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.

• Authors: Deshui Jia, Lin Wei, Weijie Guo, Ruopeng Zha, Meiyan Bao, Zhiao Chen, Yingjun Zhao, Chao Ge, Fangyu Zhao, Taoyang Chen, Ming Yao, Jinjun Li, Hongyang Wang, Jianren Gu, Xianghuo He
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 54 Issue 4 Pg. 1227-36 (Oct 2011) ISSN: 1527-3350 [Electronic] United States
• PMID: 21688285 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2011 American Association for the Study of Liver Diseases.

Topics

• Biopsy, Needle
• Carcinoma, Hepatocellular (genetics, pathology)
• Case-Control Studies
• Female
• Gene Expression Profiling (methods)
• Genes, Tumor Suppressor
• Genetic Predisposition to Disease
• Genome, Human
• Humans
• Liver Neoplasms (genetics, pathology)
• Male
• Oncogenes (genetics)
• Reference Values
• Sampling Studies
• Sensitivity and Specificity
• Tissue Culture Techniques