92 222

Cited 7 times in

Genomic copy number alterations with transcriptional deregulation at 6p identify an aggressive HCC phenotype.

Authors
Kwon, SM; Kim, DS; Won, NH; Park, SJ; Chwae, YJ; Kang, HC; Lee, SH; Baik, EJ; Thorgeirsson, SS; Woo, HG
Citation
Carcinogenesis, 34(7):1543-1550, 2013
Journal Title
Carcinogenesis
ISSN
0143-33341460-2180
Abstract
Genomic analyses have revealed the enormous heterogeneity in essentially all cancer types. However, the identification of precise subtypes, which are biologically informative and clinically useful, remains a challenge. The application of integrative analysis of multilayered genomic profiles to define the chromosomal regions of genomic copy number alterations with concomitant transcriptional deregulation is posited to provide a promising strategy to identify driver targets. In this study, we performed an integrative analysis of the DNA copy numbers and gene expression profiles of hepatocellular carcinoma (HCC). By comparing DNA copy numbers between HCC subtypes based on gene expression pattern, we revealed the DNA copy number alteration with concordant gene expression changes at 6p21-p24 particularly in the HCC subtype of aggressive phenotype without expressing stemness genes. Among the genes at 6p21-p24, we identified IER3 as a potential driver. The clinical utility of IER3 copy numbers was demonstrated by validating its clinical correlation with independent cohorts. In addition, short hairpin RNA-mediated knock-down experiment revealed the functional relevance of IER3 in liver cancer progression. In conclusion, our results suggest that genomic copy number alterations with transcriptional deregulation at 6p21-p24 identify an aggressive HCC phenotype and a novel functional biomarker.
MeSH terms
Apoptosis Regulatory Proteins/genetics/metabolismCarcinoma, Hepatocellular/*genetics/pathologyCell ProliferationChromosomes, Human, Pair 6/*geneticsComparative Genomic Hybridization*DNA Copy Number VariationsDisease Progression*Gene Expression Regulation, NeoplasticHep G2 CellsHumansLiver Neoplasms/genetics/pathologyMembrane Proteins/genetics/metabolismPhenotypeRNA, Small Interfering/genetics/metabolism*Transcription, GeneticTranscriptomeTumor Markers, Biological/genetics/metabolism
DOI
10.1093/carcin/bgt095
PMID
23508637
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
최, 용준강, 호철이, 수환백, 은주우, 현구
Full Text Link
Files in This Item:
fulltext not available.txtDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse