Abstract:
:Epigenetic inactivation by aberrant DNA methylation has been reported for many microRNA genes in various human malignancies. However, relatively little is known about microRNA gene methylation in hepatocellular carcinoma (HCC). Therefore, a systematic screen for identification of aberrantly hypermethylated microRNA genes in HCC was initiated. The methylation status of 39 intergenic CpG island associated microRNA genes was analyzed in HCC cell lines (n = 7), immortalized hepatocytes (n = 2) and normal liver samples (n = 5). Subsequently, 13 differentially methylated microRNA genes were analyzed in primary human HCC samples (n = 40), benign liver tumors (n = 15) and the adjacent liver tissues employing pyrosequencing. Expression of microRNA genes was measured using quantitative real-time polymerase chain reaction (RT-PCR). In addition, DNA methylation and expression of microRNA genes were measured after DNMT1 knockdown or DNMT inhibition. Aberrant hypermethylation and concomitant reduction in expression of intergenic microRNA genes is a frequent event in human HCC: hsa-mir-9-2 (23%), hsa-mir-9-3 (50 %), hsa-mir-124-1 (20%), hsa-mir-124-2 (13%), hsa-mir-124-3 (43%), hsa-mir-129-2 (58%), hsa-mir-596 (28%) and hsa-mir-1247 (38%). Altogether, it affects 90% of the HCC specimens under study. MicroRNA gene methylation is not found in hepatocellular adenoma (n = 10) and focal nodular hyperplasia (n = 5). DNMT1 knockdown or DNMT inhibition reduced microRNA gene methylation and stimulated expression. In primary human HCC specimens hypermethylation and expression of microRNA genes showed an inverse correlation. Concordant hypermethylation of three or more microRNA genes is a highly specific marker for the detection of HCC and for poor prognosis.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Anwar SL,Albat C,Krech T,Hasemeier B,Schipper E,Schweitzer N,Vogel A,Kreipe H,Lehmann Udoi
10.1002/ijc.28068subject
Has Abstractpub_date
2013-08-01 00:00:00pages
660-70issue
3eissn
0020-7136issn
1097-0215journal_volume
133pub_type
杂志文章abstract::A correlation analysis was performed on 125 cytogenetically characterized breast cancer cases to assess the relationship between the tumor karyotype and clinicopathologic features. The carcinomas of young women had a higher modal chromosome number than those of older women. The number of chromosomal aberrations and mo...
journal_title:International journal of cancer
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abstract::Neoplastic transformation is characterised by an imbalance in favour of cell growth over programmed cell death (apoptosis). The tumour-suppressor gene p53, responsible for maintaining cell-cycle control, is mutated in the majority of human cancers. Loss of function of the target genes of p53 are therefore important in...
journal_title:International journal of cancer
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abstract::Tumour necrosis factor alpha (TNF) mRNA is detected in the macrophage infiltrate surrounding the tumour, but the cellular/molecular interactions leading to TNF gene expression in macrophages are unknown. The in vitro system in which human blood monocytes are stimulated with human cancer cells for TNF release was used ...
journal_title:International journal of cancer
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abstract::Neuroendocrine gastrointestinal tumors take up, decarboxylate and store large amounts of monoamines. Radioactive-labeled monoamines like the norepinephrine analogue meta-iodobenzylguanidine (MIBG) have been used for the imaging of neuroendocrine tumors for many years. MIBG is selectively taken up via norepinephrine tr...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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更新日期:2006-09-15 00:00:00
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journal_title:International journal of cancer
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doi:
更新日期:2000-09-15 00:00:00
abstract::Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer ca...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2018-01-15 00:00:00
abstract::Promoter hypermethylation of various tumor-related genes is extremely frequent in gastric carcinoma (GC) associated with Epstein-Barr virus (EBV). To investigate the significance of the promoter methylation in this type of GC, we examined the methylation densities of the promoter regions of p14ARF and p16INK4A in EBV-...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2004-11-01 00:00:00
abstract::G-banding analyses of 14 independently derived B-cell lymphomas showed the frequent occurrence of chromosome 15 trisomy. It was present in seven of nine spontaneous B-cell lymphomas, but in company with other trisomies, monosomies and marker chromosomes. In five carcinogen-induced primary B-cell leukemias, trisomy 15 ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910270109
更新日期:1981-01-15 00:00:00
abstract::Limited and inefficient treatment options exist for metastatic relapsed cervical cancer (MRCC), and there are currently no reliable indicators to guide therapeutic selection. We performed deep sequencing analyses targeting 322 cancer-related genes in plasma cell-free DNA and matched white blood cells in 173 serial blo...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2021-02-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25746
更新日期:2011-08-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.20771
更新日期:2005-04-10 00:00:00
abstract::Recent epidemiological investigations have reported on the association between telomere length (TL) and a number of malignancies, including B-cell lymphoma (BCL). The reported results for BCLs are however inconsistent. We carried out a nested case-control study to determine whether TL is associated with future risk of...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28934
更新日期:2014-12-15 00:00:00
abstract::Marked variation in phenotypic expression among BRCA1 and BRCA2 mutation carriers may be partly explained by modifier genes that influence mutation penetrance. Variation in CAG/CAA repeat lengths coding for stretches of glutamines in the C-terminus of the AIB1 protein (amplified in breast cancer 1, a steroid receptor ...
journal_title:International journal of cancer
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更新日期:2005-11-01 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
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abstract::The p53 tumor suppressor pathway is impaired in more than 90% of cervical cancers and cancer-derived cell lines as a result of infection by human papillomavirus (HPV). The HPV E6 oncoprotein forms complexes with p53 and promotes its degradation via ubiquitin-dependent mechanism. In our study, we attempted to improve t...
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