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An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: CGH

ABSTRACT: This study was undertaken to identify novel tumour suppressor genes in lung adenocarcinoma. EYA4, located at 6q23.2 was identified as a frequently lost and hypermethylated gene in the analyzed samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE21540 | GEO | 2010/12/31

SECONDARY ACCESSION(S): PRJNA129511

REPOSITORIES: GEO

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An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: CGH

Project description:This study was undertaken to identify novel tumour suppressor genes in lung adenocarcinoma. EYA4, located at 6q23.2 was identified as a frequently lost and hypermethylated gene in the analyzed samples. 7 Breast cancer cell lines profiled on the SMRTr array in conjunction with matched DNA methylation data, allelic status and gene expression data for integrative analysis.

2010-12-31 | E-GEOD-21540 | biostudies-arrayexpress

EYA4 is a non-small cell lung cancer tumor suppressor located in the susceptibility locus on chromosome 6q

2014-02-25 | GSE19034 | GEO

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer.

Project description:BackgroundGenomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated derivation of predictive and prognostic signatures. The emergence of technologies for the high resolution and genome-wide description of genetic and epigenetic features has enabled the identification of a multitude of causal DNA events in tumors. This has afforded the potential for large scale integration of genome and transcriptome data generated from a variety of technology platforms to acquire a better understanding of cancer.ResultsHere we show how multi-dimensional genomics data analysis would enable the deciphering of mechanisms that disrupt regulatory/signaling cascades and downstream effects. Since not all gene expression changes observed in a tumor are causal to cancer development, we demonstrate an approach based on multiple concerted disruption (MCD) analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would be overlooked in single genomic dimension investigations.ConclusionsNotably, this is the first comprehensive study of breast cancer cells by parallel integrative genome wide analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Our findings demonstrate the power of a multi-dimensional approach to elucidate events which would escape conventional single dimensional analysis and as such, reduce the cohort sample size for cancer gene discovery.

| S-EPMC2880289 | biostudies-literature

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer

Project description:This SuperSeries is composed of the following subset Series: GSE17768: An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: gene expression GSE17769: An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: DNA methylation GSE21347: An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: allelic status GSE21540: An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: CGH Refer to individual Series

2010-12-31 | E-GEOD-21541 | biostudies-arrayexpress

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2010-12-31 | GSE21541 | GEO

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: allelic status

Project description:dChip analysis of 9 breast cancer cell lines. Data obtained from caBIG Part of a multi-dimensional analysis of gene copy number, allelic status, DNA methylation and gene expression data

2010-12-31 | E-GEOD-21347 | biostudies-arrayexpress

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: gene expression

Project description:10 Breast cancer cell lines profiled on the Affymetrix U133 Plus 2.0 platform used in conjunction with matched DNA copy number and DNA methylation data for integrative analysis. In total, 10 samples were used. The MCF10A profile used as normal was obtained from GSM254525 and the remaining 2 cell lines were obtained from caBIG. Full RMA normalized expression profile is attached.

2010-11-05 | E-GEOD-17768 | biostudies-arrayexpress

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: DNA methylation

Project description:Methylation profiles of a panel of breast cancer lines that were included in the integrative analysis of DNA copy number, allelic status, DNA methylation and gene expression. Methylation profiles of 9 breast cancer cell lines and one normal line were generated. Genes were determined to be hyper and hypomethylation in a cell line with respect to the normal line, MCF10A.

2010-11-05 | E-GEOD-17769 | biostudies-arrayexpress

EYA4 is a non-small cell lung cancer tumor suppressor located in the susceptibility locus on chromosome 6q

Project description:This study was undertaken to identify novel tumour suppressor genes in lung adenocarcinoma. EYA4, located at 6q23.2 was identified as a frequently lost and hypermethylated gene in the analyzed samples. EYA4 is underexpressed in addition to being deleted and hypermethylated. Control of EYA4 expression by DNA methylation was assessed using 5'-azacytidine. The role of EYA4 in apoptosis was assessed using a stable knock down of the gene which was assessed for apoptotis using FACS and qPCR. Methylation profiling: 30 adenocarcinoma samples and 30 patient-matched non-malignant lung samples are included. Non-malignant samples were used as references to identify hypermethylated probes. For each normal/tumor pair, the sample numbers are paired but offset by one with the tumor being the lower of the two numbers. For example, 85040001 is the adenocarcinoma tumor profile that pairs with non-malignant 85040002. Genome variation (aCGH) profiling: 30 adenocarcinoma gene dosage profiles are included. Values presented are log2 ratios of Cy3(sample)/Cy5(diploid reference)

2014-02-25 | E-GEOD-19034 | biostudies-arrayexpress

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: DNA methylation

Project description:Methylation profiles of a panel of breast cancer lines that were included in the integrative analysis of DNA copy number, allelic status, DNA methylation and gene expression.

2010-11-05 | GSE17769 | GEO

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