High-density single-nucleotide polymorphism (SNP) selleck screening library arrays now provide the possibility of defining genome-wide copy number changes.8, 9 Additionally, there has been little progress in determining specific genes targeted by various common copy number gains and losses, in part due to limited availability of complementary transcriptional data on sufficient numbers of specimens to focus on a small list of candidate genes. Although
several studies have been conducted to define potential cancer genes through combined analyses of genomic alterations and transcriptomes in HCC, they are constrained by the use of different sets and small sizes of tumor samples or by the use of relatively lower-resolution platforms.10-12 In this study we applied a whole-genome SNP 6.0 array to define a comprehensive copy number profile of 58 paired HCC and nontumor tissues. We further identified potential cancer genes by adopting a combined approach to define somatic CNAs and transcriptomes in the same set of paired HCC specimens. AFP, alpha-fetoprotein; CNA, copy number alteration; DEG, differentially expressed gene; HCC, hepatocellular carcinoma; HEY1, hairy/enhancer-of-split related with YRPW motif 1; IHC, immunohistochemistry; q-PCR, quantitative real-time polymerase chain reaction;
siRNA, small interfering RNA; SNP, single nucleotide polymorphism; SNRPE, small nuclear ribonucleoprotein polypeptide E; TRIM35, tripartite
motif-containing 35. Methods and JQ1 any associated references are available in the Supporting Materials. We analyzed the hybridization signal intensities of 58 paired HCC and nontumor tissues from the same individuals to identify regions of somatically generated CNAs. A total of 2,206 CNAs were identified in the 58 HCC genomes. A genome-wide view of segmented copy numbers revealed that most chromosomal arms undergo either see more copy number gain or loss in a large proportion of the samples (Fig. 1A). The 2,206 CNAs spanned from 0.28 kb to 30 Mb in size (median, 6.22 Mb). There was a mean of 38 CNAs per HCC genome and copy number gains were more commonly observed than losses (1.9:1). To find evidence of driver alterations in tumor genomes we further evaluated the recurrent regions of copy number gains and losses using the following parameters: the minimum physical length of putative CNAs was more than 100 kb; the CNAs was present in at least three tumor samples; and finally, the overlapping common regions among multiple tumors were calculated. Accordingly, a total of 1,241 significant CNAs were obtained, including 963 amplifications and 278 deletions (Fig. 1B). These regions were highly concordant with previous findings, including the recurrent gains at 1q, 6p, 7q, 8q, 11q, 17q, and 20q and recurrent losses at 4q, 8p, 16q, and 17p.