Down-regulation of ATBF1 is a major inactivating mechanism in hepatocellular carcinoma

C J Kim1, J H Song, Y G Cho

  • 1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Histopathology
|March 4, 2008
PubMed
Abstract

Insights

The ATBF1 gene may contribute to hepatocellular carcinoma (HCC) development by reducing its mRNA expression. Genetic or epigenetic changes in the ATBF1 gene were not found to be the cause of HCC in this study.

Area of Science:

  • Hepatology
  • Molecular Oncology
  • Cancer Genetics

Background:

  • Alpha-fetoprotein (AFP) is a marker for hepatocellular carcinoma (HCC).
  • AT motif binding factor 1 (ATBF1) normally down-regulates AFP and inhibits cell growth.
  • Altered ATBF1 gene expression is linked to malignant transformation.

Purpose of the Study:

  • To investigate the role of the ATBF1 gene in the development of hepatocellular carcinoma (HCC).

Main Methods:

  • Analysis of somatic mutations, allelic loss, and hypermethylation of the ATBF1 gene in 76 HCC samples.
  • Quantitative real-time reverse transcriptase-polymerase chain reaction to measure ATBF1 mRNA expression.

Main Results:

  • No somatic mutations were found in the ATBF1 hotspot region.
  • Allelic loss of ATBF1 was observed in 25% of informative cases.
  • Hypermethylation was detected in only one case.
  • Significantly reduced ATBF1 mRNA expression was found in 72.4% of HCCs compared to surrounding liver tissue.
  • Reduced ATBF1 expression was not associated with clinicopathological parameters.

Conclusions:

  • The ATBF1 gene may contribute to HCC development through transcriptional down-regulation of its mRNA expression.
  • Genetic or epigenetic alterations of the ATBF1 gene are unlikely to be the primary drivers of HCC.

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