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Gene expression profiles in breast cancer: breast cancer tissues vs. normal breast tissues

ABSTRACT: To screen candidate methylation markers for early detection of breast cancer, we performed methylated-CpG island recovery assay combined with CpG island array on 61982 CpG sites across 4162 genes in 10 breast tumor tissues and 10 non-tumor breast tissues. We detected 70 significantly hypermethylated genes in breast tumor tissues, including many novel hypermethylated genes such as ITGA4, NFIX, OTX2 and FGF12. Direct bisulfite sequencing showed widespread methylations occurred in intragenic regions of WT1, PAX6 and ITGA4 genes and promoter region of OTX2 in breast cancer tissue. COBRA assay in independent tumor and non-tumor samples confirmed that WT1, OTX2 and PAX6 genes were hypermethylated in breast cancer tissues. To explore the relationship between methylation and gene expression, gene expression profiling analysis was performed in 8 breast tumor tissues and 8 non-tumor breast tissues. We found that some hypermethylated genes in breast cancer were not expressed in breast tissues. RT-PCR assay showed that WT1 and PITX2 were only weakly expressed in the breast tumor tissues and weren’t expressed in most non-tumor breast tissues. OTX2 and PAX6 weren’t expressed in both breast tumor tissues and non-tumor tissues.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33447 | GEO | 2011/11/11

SECONDARY ACCESSION(S): PRJNA154301

REPOSITORIES: GEO

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Gene expression profiles in breast cancer: breast cancer tissues vs. normal breast tissues

Project description:To screen candidate methylation markers for early detection of breast cancer, we performed methylated-CpG island recovery assay combined with CpG island array on 61982 CpG sites across 4162 genes in 10 breast tumor tissues and 10 non-tumor breast tissues. We detected 70 significantly hypermethylated genes in breast tumor tissues, including many novel hypermethylated genes such as ITGA4, NFIX, OTX2 and FGF12. Direct bisulfite sequencing showed widespread methylations occurred in intragenic regions of WT1, PAX6 and ITGA4 genes and promoter region of OTX2 in breast cancer tissue. COBRA assay in independent tumor and non-tumor samples confirmed that WT1, OTX2 and PAX6 genes were hypermethylated in breast cancer tissues. To explore the relationship between methylation and gene expression, gene expression profiling analysis was performed in 8 breast tumor tissues and 8 non-tumor breast tissues. We found that some hypermethylated genes in breast cancer were not expressed in breast tissues. RT-PCR assay showed that WT1 and PITX2 were only weakly expressed in the breast tumor tissues and weren’t expressed in most non-tumor breast tissues. OTX2 and PAX6 weren’t expressed in both breast tumor tissues and non-tumor tissues. Unpaired experiments, breast tumor tissues vs. breast non-tumor tissues. Biological replicates: 8 breast cancer tissue replicates, 8 breast non-tumor tissue replicates.

2011-11-11 | E-GEOD-33447 | biostudies-arrayexpress

DNA hypermethylation in breast cancer: breast cancer tissues vs. normal breast tissues

Project description:To screen candidate methylation markers for early detection of breast cancer, we performed methylated-CpG island recovery assay combined with CpG island array on 61982 CpG sites across 4162 genes in 10 breast tumor tissues and 10 non-tumor breast tissues. We detected 70 significantly hypermethylated genes in breast tumor tissues, including many novel hypermethylated genes such as ITGA4, NFIX, OTX2 and FGF12. Direct bisulfite sequencing showed widespread methylations occurred in intragenic regions of WT1, PAX6 and ITGA4 genes and promoter region of OTX2 in breast cancer tissue. COBRA assay in independent tumor and non-tumor samples confirmed that WT1, OTX2 and PAX6 genes were hypermethylated in breast cancer tissues. To explore the relationship between methylation and gene expression, gene expression profiling analysis was performed in 8 breast tumor tissues and 8 non-tumor breast tissues. We found that some hypermethylated genes in breast cancer were not expressed in breast tissues. RT-PCR assay showed that WT1 and PITX2 were only weakly expressed in the breast tumor tissues and weren’t expressed in most non-tumor breast tissues. OTX2 and PAX6 weren’t expressed in both breast tumor tissues and non-tumor tissues. Unpaired experiments, breast cancer tissue vs. normal cancer tissue. Biological replicates: 10 breast cancer tissue replicates, 10 normal breast tissue replicates.

2011-11-11 | E-GEOD-33445 | biostudies-arrayexpress

DNA hypermethylation in breast cancer: breast cancer tissues vs. normal breast tissues

2011-11-11 | GSE33445 | GEO

DNA methylation profiling in the Carolina Breast Cancer Study

Project description:A microarray targeting promoters of cancer-related genes was used to evaluate DNA methylation at 935 CpG sites in 517 invasive breast tumors from the Carolina Breast Cancer Study (CBCS), a population-based study of invasive breast cancer. Concensus clustering using methylation (β) values for the 167 most variant CpG loci defined 4 clusters differing most distinctly in hormone receptor (HR) status, intrinsic subtype (luminal versus basal-like) and p53 mutation status. Supervised analyses for HR status, subtype, and p53 status identified differentially methylated CpG loci with considerable overlap (n=266). Concensus clustering also defined a hypermethylated luminal-enriched tumor cluster 3; gene ontology analysis of cluster 3 hypermethylated loci revealed enrichment for developmental genes, including homeobox domain genes (HOXB13, PAX6, IPF1, EYA4, DLK1, IHH, ISL1, TBX1, SOX1, SOX17). The hypermethylated luminal-enriched cluster 3 independently predicted poorer survival in multivariate Cox proportional hazard analysis, and this finding was confirmed in analysis of luminal A tumors. This study demonstrates epigenetic heterogeneity among breast tumors of a single intrinsic subtype, and shows that epigenetic patterns are strongly associated with HR status, subtype, and p53 mutation status. Among HR+ tumors, a gene signature characterized by hypermethylation of developmental genes may have prognostic value. Genes differentially methylated between clinically-important tumor subsets have roles in differentiation, development, and tumor growth and may be critical to inducing and maintaining tumor phenotypes and clinical outcomes. 517 breast tumors, 9 normal breast tissues

2015-04-07 | E-GEOD-51557 | biostudies-arrayexpress

Exploring genome-wide DNA methylation profiles altered in hepatocellular carcinoma using Infinium HumanMethylation 450 BeadChips

2014-01-30 | GSE54503 | GEO

Exploring genome-wide DNA methylation profiles altered in hepatocellular carcinoma using Infinium HumanMethylation 450 BeadChips

Project description:We examine genome-wide DNA methylation profiles in 66 pairs of HCC tumor and adjacent non-tumor tissues. After Bonferroni adjustment, a total of 130,512 CpG sites significantly differed in methylation level in tumor compared to non-tumor tissues, with 28,017 CpG sites hypermethylated and 102,495 hypomethylated in tumor tissues. Most (60.1%) significantly hypermethylated CpG sites are located in CpG islands. These results demonstrate the significance of aberrant DNA methylation in HCC tumorigenesis. Bisulfite modification of 1µg DNA was conducted using an EZ DNA Methylation Kit (Zymo Research, Irvine, CA) according to the manufacturer’s procedure. The Infinium Methylation 450K assay was performed according to Illumina’s standard protocol. Six HCC tumor/adjacent non-tumor tissue pairs were processed on the same chip to avoid chip-to-chip variation.

2014-01-30 | E-GEOD-54503 | biostudies-arrayexpress

DNA methylation profiling in the Carolina Breast Cancer Study

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Methylation in Taiwanese HCC tumor and adjacent tissues

Project description:We analyzed tumor and adjacent non-tumor tissues from 62 Taiwanese HCC cases using Illumina HumanMethylation 27 chips. After Bonferroni adjustment, a total of 2,324 CpG sites significantly differed in methylation level, with 684 CpG sites significantly hypermethylated and 1,640 hypomethylated in tumor compared to non-tumor tissues. Array data were validated with pyrosequencing in a subset of 5 of these genes; correlation coefficients ranged from 0.92 to 0.97. 62 tumor and 62 adjacent non tumor tissues

2012-05-15 | E-GEOD-37988 | biostudies-arrayexpress

Methylation in Taiwanese HCC tumor and adjacent tissues

2012-05-16 | GSE37988 | GEO

DNA hypermethylation in colorectal cancer: Colorectal cancer tissues vs. Adjacent non-tumor tissues

Project description:To identify novel hypermethylated genes in colorectal cancer (CRC) and to test their potential application in CRC early diagnosis, we performed a genome-wide screening of 57,723 CpG dinucleotides covering 4,010 genes in paired DNA samples extracted from 3 fresh frozen CRC tissues and their matching non-tumor adjacent tissues from a cohort of 3 CRC patients undergoing curative surgery using MIRA-based microarray. We also validated candidate hypermethylated genes screened by MIRA-based microarray in independent CRC samples using combined bisulfite restriction analysis. A total of 297 CpG dinucleotides in CRC covering 211 genes were found to be hypermethylated in CRC tissues. From these 211 candidate methylated genes, seven novel methylated genes were picked up for validation and three genes were confirmed to be methylated in cancer samples but not in non-cancer samples.We also compared the methylation levels of these three novel hypermethylated genes with those of Vimentin and SEPT9, well-known hypermethylated genes in CRC, and found that methylated PHOX2B, FGF12 and GAD2 were better than methylated Vimentin and SEPT9 in differentiating CRC cancer tissue from normal tissue. Significant enrichment analysis of GO terms of the hypermethylated genes showed that a high proportion of hypermethylated genes in tumor tissues are involved in regulation of transcription. Paired experiments, colorectal cancer tissue vs. adjacent non-cancer tissue. Biological replicates: 3 cancer replicates, 3 paired non-cancer replicates.

2011-11-14 | E-GEOD-33545 | biostudies-arrayexpress

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