title: Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma.
abstract: High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma (HCC) cohorts confirmed previously identified frequently mutated somatic genes, such as TP53, CTNNB1 and AXIN1, and identified several novel genes with moderate mutation frequencies, including ARID1A, ARID2, MLL, MLL2, MLL3, MLL4, IRF2, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3, JAK1, KEAP1, NFE2L2, C16orf62, LEPR, RAC2, and IL6ST. Functional classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling, Wnt/β-catenin signaling, JAK/STAT signaling, and oxidative stress play critical roles in HCC tumorigenesis. Nevertheless, because there are few druggable genes used in HCC therapy, the identification of new therapeutic targets through integrated genomic approaches remains an important task. Because a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain, copy number alteration (CNA) analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons, homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC progression. Moreover, integration of CNAs with other high-throughput genomic data, such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models, provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients.
authors.affiliation: De-Leung Gu, Yen-Hsieh Chen, Jou-Ho Shih, Yuh-Shan Jou, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: De-Leung
authors.initials: DL
authors.lastname: Gu
authors.affiliation: De-Leung Gu, Yen-Hsieh Chen, Jou-Ho Shih, Yuh-Shan Jou, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yen-Hsieh
authors.initials: YH
authors.lastname: Chen
authors.affiliation: De-Leung Gu, Yen-Hsieh Chen, Jou-Ho Shih, Yuh-Shan Jou, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Jou-Ho
authors.initials: JH
authors.lastname: Shih
authors.affiliation: De-Leung Gu, Yen-Hsieh Chen, Jou-Ho Shih, Yuh-Shan Jou, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: De-Leung Gu, Yen-Hsieh Chen, Jou-Ho Shih, Yuh-Shan Jou, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.affiliation: De-Leung Gu, Yen-Hsieh Chen, Jou-Ho Shih, Yuh-Shan Jou, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Chian-Feng
authors.initials: CF
authors.lastname: Chen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
keywords: Copy number alteration; Driver genes; Hepatocellular carcinoma; High-density single nucleotide polymorphism arrays