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Published on: June 3, 2016
Down-regulation of ATBF1 is a major inactivating mechanism in hepatocellular carcinoma
1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Aims:
alpha-Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down-regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs.
Methods And Results:
Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF-1 mRNA expression was analysed using quantitative real-time reverse transcriptase-polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum alpha-fetoprotein level.
Conclusions:
The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations.
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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