ArticleJournal of gastroenterology2013
Loss of heterozygosity and methylation of multiple tumor suppressor genes on chromosome 3 in hepatocellular carcinoma.
Article in Journal of gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular carcinoma: a meta-analysis of 21 cohort studies.Molecular biology reports · 2014Pooled it
- Association between Ras association domain family 1A promoter methylation and hepatocellular carcinoma: a meta-analysis.World journal of gastroenterology · 2013Pooled it
- Integrated and clinical validation of helicase-like transcription factor as a biomarker for hepatocellular carcinoma.BMC cancer · 2026Article
- CD137L promotes immune surveillance in melanoma via HLTF regulation.Nature communications · 2025Article
- Upregulation of helicase-like transcription factor predicts poor prognosis and facilitates hepatocellular carcinoma progression.Human cell · 2023Article
- Degradation of helicase-like transcription factor (HLTF) by β-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis.Journal of molecular cell biology · 2023Article
- HLTF promotes hepatocellular carcinoma progression by enhancing SRSF1 stability and activating ERK/MAPK pathway.Oncogenesis · 2023Article
- Diagnosis and staging of HCV associated fibrosis, cirrhosis and hepatocellular carcinoma with target identification for miR-650, 552-3p, 676-3p, 512-5p and 147b.Cancer biomarkers : section A of Disease markers · 2022Article
- Identification of RASSF1A promoter hypermethylation as a biomarker for hepatocellular carcinoma.Cancer cell international · 2020Article
- Genome Profiling for Aflatoxin BG3 (Bethesda, Md.) · 2020Article
- The ubiquitous 'cancer mutational signature' 5 occurs specifically in cancers with deletedOncotarget · 2017Article
- FHIT promoter DNA methylation and expression analysis in childhood acute lymphoblastic leukemia.Oncology letters · 2017Article
- Association of FHIT expression andOncoTargets and therapy · 2017Article
- Article
- The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor?Cellular and molecular life sciences : CMLS · 2016Review
- PCDH8 is Frequently Inactivated by Promoter Hypermethylation in Liver Cancer: Diagnostic and Clinical Significance.Journal of Cancer · 2016Article
- Differential methylation of the promoter and first exon of the RASSF1A gene in hepatocarcinogenesis.Hepatology research : the official journal of the Japan Society of Hepatology · 2015Article
- Functional characterization of the nitrogen permease regulator-like-2 candidate tumor suppressor gene in colorectal cancer cell lines.Molecular medicine reports · 2015Article
- Frequent SOCS3 and 3OST2 promoter methylation and their epigenetic regulation in endometrial carcinoma.American journal of cancer research · 2015Article
- Gene expression profiling to predict and assess the consequences of therapy-induced virus eradication in chronic hepatitis C virus infection.Journal of virology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic and epigenetic alterations are the two key mechanisms in the development of hepatocellular carcinoma (HCC). However, how they contribute to hepatocarcinogenesis and the correlation between them has not been fully elucidated.
methodsA total of 48 paired HCCs and noncancerous tissues were used to detect loss of heterozygosity (LOH) and the methylation profiles of five tumor suppressor genes (RASSF1A, BLU, FHIT, CRBP1, and HLTF) on chromosome 3 by using polymerase chain reaction (PCR) and methylation-specific PCR. Gene expression was analyzed by immunohistochemistry and reverse transcription (RT)-PCR.
resultsSixteen of 48 (33.3 %) HCCs had LOH on at least one locus on chromosome 3, and two smallest common deleted regions (3p22.3-24.3 and 3p12.3-14.2) were identified. RASSF1A, BLU, and FHIT showed very high frequencies of methylation in HCCs (100, 81.3, and 64.6 %, respectively) and noncancerous tissues, but not in liver tissues from control patients. Well-differentiated HCCs showed high methylation frequencies of these genes but very low frequencies of LOH. Furthermore, BLU methylation was associated with an increased level of alpha-fetoprotein, and FHIT methylation was inversely correlated with HCC recurrence. In comparison, CRBP1 showed moderate frequencies of methylation, while HLTF showed low frequencies of methylation, and CRBP1 methylation occurred mainly in elderly patients. Treatment with 5-aza-2'-deoxycytidine demethylated at least one of these genes and restored their expression in a DNA methylation-dependent or -independent manner.
conclusionsHypermethylation of RASSF1A, BLU, and FHIT is a common and very early event in hepatocarcinogenesis; CRBP1 methylation may also be involved in the later stage. Although LOH was not too frequent on chromosome 3, it may play a role as another mechanism in hepatocarcinogenesis.
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