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

Pal Kaposi-Novak; Louis Libbrecht; Hyun Goo Woo; Yun-Han Lee; Nathaniel C Sears; Cedric Coulouarn; Elizabeth A Conner; Valentina M Factor; Tania Roskams; Snorri S Thorgeirsson

doi:10.1158/0008-5472.CAN-08-3357

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

Journal article

Open access

Peer reviewed

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

Pal Kaposi-Novak, Louis Libbrecht, Hyun Goo Woo, Yun-Han Lee, Nathaniel C Sears, Cedric Coulouarn, Elizabeth A Conner, Valentina M Factor, Tania Roskams and Snorri S Thorgeirsson

Cancer research (Chicago, Ill.), Vol.69(7), pp.2775-2782

04/01/2009

DOI: 10.1158/0008-5472.CAN-08-3357

PMCID: PMC2680077

PMID: 19276364

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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.

Liver Neoplasms - genetics

Humans

Gene Expression Regulation, Neoplastic

Precancerous Conditions - metabolism

Gene Expression Profiling

Genes, myc

Cell Transformation, Neoplastic - metabolism

Precancerous Conditions - genetics

Disease Progression

Proto-Oncogene Proteins c-myc - biosynthesis

Cell Transformation, Neoplastic - genetics

Carcinoma, Hepatocellular - genetics

Carcinoma, Hepatocellular - pathology

Liver Cirrhosis - metabolism

Liver Neoplasms - metabolism

Liver Cirrhosis - pathology

Liver Neoplasms - pathology

Precancerous Conditions - pathology

Proto-Oncogene Proteins c-myc - genetics

Cell Transformation, Neoplastic - pathology

Neoplasm Staging

Liver Cirrhosis - genetics

Carcinoma, Hepatocellular - metabolism

Details

Title: Subtitle: Central role of c-Myc during malignant conversion in human hepatocarcinogenesis
Creators: Pal Kaposi-Novak - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Center for Cancer Research, NIH, Bethesda, Maryland 20892, USA
Louis Libbrecht
Hyun Goo Woo
Yun-Han Lee
Nathaniel C Sears
Cedric Coulouarn
Elizabeth A Conner
Valentina M Factor
Tania Roskams
Snorri S Thorgeirsson
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.69(7), pp.2775-2782
Publisher: United States
DOI: 10.1158/0008-5472.CAN-08-3357
PMID: 19276364
PMCID: PMC2680077
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: Z99 CA999999 / Intramural NIH HHS
Language: English
Date published: 04/01/2009
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983979950202771

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