title: Digital karyotyping reveals probable target genes at 7q21.3 locus in hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a worldwide malignant liver tumor with high incidence in China. Subchromosomal amplifications and deletions accounted for major genomic alterations occurred in HCC. Digital karyotyping was an effective method for analyzing genome-wide chromosomal aberrations at high resolution.
  
  
  METHODS
  A digital karyotyping library of HCC was constructed and 454 Genome Sequencer FLX System (Roche) was applied in large scale sequencing of the library. Digital Karyotyping Data Viewer software was used to analyze genomic amplifications and deletions. Genomic amplifications of genes detected by digital karyotyping were examined by real-time quantitative PCR. The mRNA expression level of these genes in tumorous and paired nontumorous tissues was also detected by real-time quantitative RT-PCR.
  
  
  RESULTS
  A total of 821,252 genomic tags were obtained from the digital karyotyping library of HCC, with 529,162 tags (64%) mapped to unique loci of human genome. Multiple subchromosomal amplifications and deletions were detected through analyzing the digital karyotyping data, among which the amplification of 7q21.3 drew our special attention. Validation of genes harbored within amplicons at 7q21.3 locus revealed that genomic amplification of SGCE, PEG10, DYNC1I1 and SLC25A13 occurred in 11 (21%), 11 (21%), 11 (21%) and 23 (44%) of the 52 HCC samples respectively. Furthermore, the mRNA expression level of SGCE, PEG10 and DYNC1I1 were significantly up-regulated in tumorous liver tissues compared with corresponding nontumorous counterparts.
  
  
  CONCLUSIONS
  Our results indicated that subchromosomal region of 7q21.3 was amplified in HCC, and SGCE, PEG10 and DYNC1I1 were probable protooncogenes located within the 7q21.3 locus.
authors.affiliation: Chinese National Human Genome Center at Shanghai, Shanghai 201203, China. dongh@chgc.sh.cn
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Liang
authors.forename: Huadong
authors.initials: H
authors.lastname: Yan
authors.forename: Yangyi
authors.initials: Y
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Yalin
authors.initials: Y
authors.lastname: Kong
authors.forename: Shengyue
authors.initials: S
authors.lastname: Wang
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
authors.forename: Weirong
authors.initials: W
authors.lastname: Jin
mesh_terms: D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D056445:Cytoplasmic Dyneins / Q000235:genetics; D004268:DNA-Binding Proteins; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D049031:Sarcoglycans / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C432965:PEG10 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; C526572:SGCE protein, human; D049031:Sarcoglycans; C424131:DYNC1LI1 protein, human; D056445:Cytoplasmic Dyneins