title: Genome-wide copy number analyses identified novel cancer genes in hepatocellular carcinoma.
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.
  
  
  CONCLUSIONS
  These results showed that integration of genomic and transcriptional data offers powerful potential for identifying novel cancer genes in HCC pathogenesis.
authors.affiliation: Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Deshui
authors.initials: D
authors.lastname: Jia
authors.forename: Lin
authors.initials: L
authors.lastname: Wei
authors.forename: Weijie
authors.initials: W
authors.lastname: Guo
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Zha
authors.forename: Meiyan
authors.initials: M
authors.lastname: Bao
authors.forename: Zhiao
authors.initials: Z
authors.lastname: Chen
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Ge
authors.forename: Fangyu
authors.initials: F
authors.lastname: Zhao
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
mesh_terms: D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009857:Oncogenes / Q000235:genetics; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques