364 200

Cited 119 times in

Central role of c-Myc during malignant conversion in human hepatocarcinogenesis

Authors
 Pal Kaposi-Novak  ;  Louis Libbrecht  ;  Hyun-Goo Woo  ;  Yun-Han Lee  ;  Nathaniel C. Sears  ;  Elizabeth A. Conner  ;  Valentina M. Factor  ;  Tania Roskams  ;  Snorri S. Thorgeirsson 
Citation
 CANCER RESEARCH, Vol.69(7) : 2775-2782, 2009 
Journal Title
 CANCER RESEARCH 
ISSN
 0008-5472 
Issue Date
2009
MeSH
Carcinoma, Hepatocellular/genetics* ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Transformation, Neoplastic/genetics* ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, myc* ; Humans ; Liver Cirrhosis/genetics ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; Liver Neoplasms/genetics* ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Neoplasm Staging ; Precancerous Conditions/genetics ; Precancerous Conditions/metabolism ; Precancerous Conditions/pathology ; Proto-Oncogene Proteins c-myc/biosynthesis* ; Proto-Oncogene Proteins c-myc/genetics
Abstract
Hepatocarcinogenesis is a multistage process in which precursor lesions progress into early hepatocellular carcinomas (eHCC) by sequential accumulation of multiple genetic and epigenetic alterations. To decode the molecular events during early stages of liver carcinogenesis, we performed gene expression profiling on cirrhotic (regenerative) and dysplastic nodules (DN), as well as eHCC. Although considerable heterogeneity was observed at the regenerative and dysplastic stages, overall, 460 differentially expressed genes were detected between DN and eHCC. Functional analysis of the significant gene set identified the MYC oncogene as a plausible driver gene for malignant conversion of the DNs. in addition, gene set enrichment analysis revealed global activation of the MYC up-regulated gene set in eHCC versus dysplasia. Presence of the MYC signature significantly correlated with increased expression of CSN5, as well as with higher overall transcription rate of genes located in the 8q chromosome region. Furthermore, a classifier constructed from MYC target genes could robustly discriminate eHCC from high-grade and low-grade DNs. in conclusion, our study identified unique expression patterns associated with the transition of high-grade DNs into eHCC and showed that activation of the MYC transcription signature is strongly associated with the malignant conversion of preneoplastic liver lesions.
Files in This Item:
T200906248.pdf Download
DOI
10.1158/0008-5472.CAN-08-3357
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Lee, Yun Han(이윤한)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106086
사서에게 알리기
  feedback

qrcode

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

Browse

Links