Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor-suppressor in hepatocellular carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE35313 | GEO | 2012/03/31
SECONDARY ACCESSION(S): PRJNA150743
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE35311: Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor-suppressor in hepatocellular carcinoma (expression) GSE35312: Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor-suppressor in hepatocellular carcinoma (MeDIP) Refer to individual Series
2012-03-30 | E-GEOD-35313 | biostudies-arrayexpress
Project description:The analysis of DNA methylation profiles was performed by methylated DNA immunoprecipitation (MeDIP) using anti-5-methylcytidine antibody (Eurogentec, Seraing, Belgium) followed by the Human 244K Agilent CpG island microarray (Agilent, Santa Clara, CA)
2012-03-31 | GSE35312 | GEO
Project description:Gene expression was profiled using a 4x44K Human Whole Genome Ver. 2.0 gene expression array (Agilent Technologies) according to the manufacturer's instructions (Microarray-based gene expression analysis protocol ver. 5.0.1, Agilent Technologies)
2012-03-31 | GSE35311 | GEO
Project description:The analysis of DNA methylation profiles was performed by methylated DNA immunoprecipitation (MeDIP) using anti-5-methylcytidine antibody (Eurogentec, Seraing, Belgium) followed by the Human 244K Agilent CpG island microarray (Agilent, Santa Clara, CA) Genomic DNAs from Hep3B, HepG2 and HuH-7 cells were used for cancer samples and that from a normal liver tissue from surgical sample of colon cancer metastasis, as a control sample (C20)
2012-03-30 | E-GEOD-35312 | biostudies-arrayexpress
Project description:Gene expression was profiled using a 4x44K Human Whole Genome Ver. 2.0 gene expression array (Agilent Technologies) according to the manufacturer's instructions (Microarray-based gene expression analysis protocol ver. 5.0.1, Agilent Technologies) Total RNAs extracted from Hep3B, HepG2, and HuH-7 cell lines and from these cell lines treated with 10 ?M 5-aza-dCyd for 5 days were used for conventional and pharmacological unmasking analyses, respectively. Total RNAs from two normal livers (C20 and C40) were used as controls.
2012-03-30 | E-GEOD-35311 | biostudies-arrayexpress
Project description:Promoter region hyermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty-eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) showed frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM and SFRP1 suppressed the growth of RCC cell lines and RNA interference knock-down of BNC1, SFRP1 and COL14A1 increased the growth of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC TSGs can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection.
| S-EPMC3021900 | biostudies-literature
Project description:IntroductionMetastasis represents a major adverse step in the progression of breast carcinoma. Lymph node invasion is the most relevant prognostic factor; however little is known on the molecular events associated with lymph node metastasis process. This study is to investigate the status and role of methylation in lymph node metastatic tumors.Materials and methodsBisulfite pyrosequencing is used to screen 6 putative tumor suppressor genes (HIN-1, RASSF1A, RIL, CDH13, RARbeta2 and E-cadherin) in 38 pairs of primary breast tumors and lymph node metastases.ResultsWe found that HIN-1, CDH13, RIL, RASSF1A and RARbeta2 were frequently methylated both in primary and metastatic tissues (range: 55.3% approximately 89.5%). E-cadherin was not frequently methylated in either setting (range: 18.4% approximately 23.7%). The methylation status of HIN-1, CDH13, RIL, and RARbeta2 in lymph nodes metastasis were correlated with that in primary tumors. The Pearson correlation values ranged from 0.624 to 0.472 (p values < 0.01 to 0.001). Interestingly, we observed an association between HIN-1 methylation and hormone status in metastatic lymph nodes. Hypermethylation of HIN-1 in metastasis lymph nodes was significantly associated with expression of ER (odds ratio, 1.070; P = 0.024) and with PR (odds ratio, 1.046; P = 0.026).ConclusionsThis study suggests that hypermethylation of tumor suppressor genes is extended from primary to metastatic tumors during tumor progression.
| S-EPMC2914707 | biostudies-literature
Project description:BackgroundGenetic as well as epigenetic alterations are a hallmark of both epithelial and haematological malignancies. High throughput screens are required to identify epigenetic markers that can be useful for diagnostic and prognostic purposes across malignancies.ResultsHere we report for the first time the use of the MIRA assay (methylated CpG island recovery assay) in combination with genome-wide CpG island arrays to identify epigenetic molecular markers in childhood acute lymphoblastic leukemia (ALL) on a genome-wide scale. We identified 30 genes demonstrating methylation frequencies of > or =25% in childhood ALL, nine genes showed significantly different methylation frequencies in B vs T-ALL. For majority of the genes expression could be restored in methylated leukemia lines after treatment with 5-azaDC. Forty-four percent of the genes represent targets of the polycomb complex. In chronic myeloid leukemia (CML) two of the genes, (TFAP2A and EBF2), demonstrated increased methylation in blast crisis compared to chronic phase (P < 0.05). Furthermore hypermethylation of an autophagy related gene ATG16L2 was associated with poorer prognosis in terms of molecular response to Imatinib treatment. Lastly we demonstrated that ten of these genes were also frequently methylated in common epithelial cancers.ConclusionIn summary we have identified a large number of genes showing frequent methylation in childhood ALL, methylation status of two of these genes is associated with advanced disease in CML and methylation status of another gene is associated with prognosis. In addition a subset of these genes may act as epigenetic markers across hematological malignancies as well as common epithelial cancers.
| S-EPMC2838813 | biostudies-literature
Project description:BACKGROUND: Human disabled-2 (DAB2), is a multi-function signalling molecule that it is frequently down-regulated in human cancers. We aimed to investigate the possible tumour suppressor effect of DAB2 in nasopharyngeal carcinoma (NPC). METHODS: We studied the expression of DAB2 in NPC cell lines, xenografts and primary tumour samples. The status of promoter methylation was assessed by methylation specific PCR and bisulfite sequencing. The functional role of DAB2 in NPC was investigated by re-introducing DAB2 expression into NPC cell line C666-1. RESULTS: Decrease or absent of DAB2 transcript was observed in NPC cell lines and xenografts. Loss of DAB2 protein expression was seen in 72% (33/46) of primary NPC as demonstrated by immunohistochemistry. Aberrant DAB2 promoter methylation was detected in 65.2% (30/46) of primary NPC samples by methylation specific PCR. Treatment of the DAB2 negative NPC cell line C666-1 with 5-aza-2'-deoxycytidine resulted in restoration of DAB2 expression in a dose-dependent manner. Overexpression of DAB2 in NPC cell line C666-1 resulted in reduced growth rate and 35% reduction in anchorage-dependent colony formation, and inhibition of serum-induced c-Fos expression compared to vector-transfected controls. Over expression of DAB2 resulted in alterations of multiple pathways as demonstrated by expression profiling and functional network analysis, which confirmed the role of DAB2 as an adaptor molecule involved in multiple receptor-mediated signalling pathways. CONCLUSIONS: We report the frequent down regulation of DAB2 in NPC and the promoter hypermethylation contributes to the loss of expression of DAB2. This is the first study demonstrating frequent DAB2 promoter hypermethylation in human cancer. Our functional studies support the putative tumour suppressor effect of DAB2 in NPC cells.
| S-EPMC2891638 | biostudies-literature
Project description:BackgroundBreast cancer is a genetically heterogeneous type of cancer that belongs to the most prevalent types with a high mortality rate. Treatment and prognosis of breast cancer would profit largely from a correct classification and identification of genetic key drivers and major determinants driving the tumorigenesis process. In the light of the availability of tumor genomic and epigenomic data from different sources and experiments, new integrative approaches are needed to boost the probability of identifying such genetic key drivers. We present here an integrative network-based approach that is able to associate regulatory network interactions with the development of breast carcinoma by integrating information from gene expression, DNA methylation, miRNA expression, and somatic mutation datasets.ResultsOur results showed strong association between regulatory elements from different data sources in terms of the mutual regulatory influence and genomic proximity. By analyzing different types of regulatory interactions, TF-gene, miRNA-mRNA, and proximity analysis of somatic variants, we identified 106 genes, 68 miRNAs, and 9 mutations that are candidate drivers of oncogenic processes in breast cancer. Moreover, we unraveled regulatory interactions among these key drivers and the other elements in the breast cancer network. Intriguingly, about one third of the identified driver genes are targeted by known anti-cancer drugs and the majority of the identified key miRNAs are implicated in cancerogenesis of multiple organs. Also, the identified driver mutations likely cause damaging effects on protein functions. The constructed gene network and the identified key drivers were compared to well-established network-based methods.ConclusionThe integrated molecular analysis enabled by the presented network-based approach substantially expands our knowledge base of prospective genomic drivers of genes, miRNAs, and mutations. For a good part of the identified key drivers there exists solid evidence for involvement in the development of breast carcinomas. Our approach also unraveled the complex regulatory interactions comprising the identified key drivers. These genomic drivers could be further investigated in the wet lab as potential candidates for new drug targets. This integrative approach can be applied in a similar fashion to other cancer types, complex diseases, or for studying cellular differentiation processes.
| S-EPMC4460623 | biostudies-literature