Transcriptome profiling of normal breast tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205725 | GEO | 2023/09/12
REPOSITORIES: GEO
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Project description:The Susan G. Komen Tissue Bank at Indiana University Simon Cancer Center (KTB) is the only repository of normal breast tissues donated by healthy women. As expected, a relatively small number of KTB donors (≈5%) diagnosed with breast cancer a few years post-donation. The specimens originally donated by these women (here labeled “susceptible normal tissue”) provide a window into the earliest phases of breast cancer development. Here, we investigated the transcriptomic changes in the histologically normal breast tissues donated by women 2-8 years prior to their diagnosis of breast cancer (mostly DCIS), as compared with breasts from age-matched healthy subjects.
2021-09-30 | GSE166044 | GEO
Project description:The Susan G. Komen Tissue Bank at Indiana University Simon Cancer Center (KTB) is the only repository of normal breast tissues donated by healthy women. As expected, a relatively small number of KTB donors (≈5%) diagnosed with breast cancer a few years post-donation. The specimens originally donated by these women (here labeled “susceptible normal tissue”) provide a window into the earliest phases of breast cancer development. Here, we investigated the DNA metylation changes in the histologically normal breast tissues donated by women 2-8 years prior to their diagnosis of breast cancer (mostly DCIS), as compared with breasts from age-matched healthy subjects.
2021-09-30 | GSE166045 | GEO
Project description:The contralateral unaffected breast of women with unilateral breast cancer (cases) is a good model for defining subtype-specific risk since women with ER-negative index primaries are at high risk for subsequent ER-negative primary cancers. We performed random fine needle aspiration (rFNA) of the unaffected breasts of cases; samples from 30 subjects (15 ER-positive and 15 ER-negative cases matched for age, race and menopausal status), were used for Illumina expression array analysis. In this study, we have examined gene expression profiles in random fine needle aspirate (rFNA) samples from the contralateral breasts of women with new unilateral breast cancer (cases) to seek candidate panels of ER-specific risk biomarkers. On a discovery set of 30 women, we have identified gene expression differences in the contralateral breast that associate with ER+ or ER- index primary tumors.
2013-03-26 | E-GEOD-41400 | biostudies-arrayexpress
Project description:Epigenetic mechanisms such as DNA methylation are important regulators of gene expression and are frequently dysregulated early in breast carcinogenesis. The relationship between DNA methylation aberrations in normal breast tissue and breast cancer risk remains unclear. Disease-free breast tissue cores donated by high-risk (Tyrer-Cuzick lifetime risk ≥20%) and 78 average-risk women were obtained from the Susan G. Komen Tissue Bank and processed for whole methylome and whole transcriptome profiling. We identified 1355 CpGs that were differentially methylated between high- and average-risk breast tissues (ΔZ>0.5, FDR<0.05). Hypomethylated CpGs were overrepresented in high-risk tissue and were found predominantly (68%) in non-coding regions. Hypermethylated CpG sites were found equally in the gene body and non-coding regions. Transcriptomic analysis identified 67 differentially expressed genes (fold change≥2, FDR<0.05, 17 down 50 up), involved in chemokines signaling, metabolism and estrogen biosynthesis. Methylation-expression correlations revealed 6 epigenetically regulated genes in high-risk breast. This is the first gene expression/DNA methylation analysis of normal breasts from women at either high or average risk of breast cancer. Our discovery of epigenetically regulated genes associated with breast cancer risk using a unique resource of normal breast samples opens the doors to a deeper understanding of the process of cancer initiation and provides an opportunity to mechanistically dissect breast cancer susceptibility and risk-associated molecular alterations.
2021-09-30 | GSE164641 | GEO
Project description:Epigenetic mechanisms such as DNA methylation are important regulators of gene expression and are frequently dysregulated early in breast carcinogenesis. The relationship between DNA methylation aberrations in normal breast tissue and breast cancer risk remains unclear. Disease-free breast tissue cores donated by high-risk (Tyrer-Cuzick lifetime risk ≥20%) and 78 average-risk women were obtained from the Susan G. Komen Tissue Bank and processed for whole methylome and whole transcriptome profiling. We identified 1355 CpGs that were differentially methylated between high- and average-risk breast tissues (ΔZ>0.5, FDR<0.05). Hypomethylated CpGs were overrepresented in high-risk tissue and were found predominantly (68%) in non-coding regions. Hypermethylated CpG sites were found equally in the gene body and non-coding regions. Transcriptomic analysis identified 67 differentially expressed genes (fold change≥2, FDR<0.05, 17 down 50 up), involved in chemokines signaling, metabolism and estrogen biosynthesis. Methylation-expression correlations revealed 6 epigenetically regulated genes in high-risk breast. This is the first gene expression/DNA methylation analysis of normal breasts from women at either high or average risk of breast cancer. Our discovery of epigenetically regulated genes associated with breast cancer risk using a unique resource of normal breast samples opens the doors to a deeper understanding of the process of cancer initiation and provides an opportunity to mechanistically dissect breast cancer susceptibility and risk-associated molecular alterations.
2021-09-30 | GSE164640 | GEO
Project description:Introduction Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Methods Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and generalized regression models were used to assess the independent contribution from different variables to MD. Results SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Conclusions Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest among young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer. Gene expression analysis of breast biopsies from 143 women, 79 non-cancer (healthy women with no cancer who had a mammogram taken) and 64 breast cancer.
2010-08-13 | E-GEOD-18672 | biostudies-arrayexpress
Project description:The tissue stroma plays a major role in tumors natural history. Important programs for tumor progression such as epithelial mesenchymal transition are not activated as cell-autonomous processes but under the conditions of cross-talk between tumor and stroma. Adipose tissue is a major component of the stroma and, because of their extended half-life, adipocytes are witnesses of tissue exposures. This study compares breast fat in women with breast tumors to those in healthy women to try to define a signature that could be translated into biomarkers for cancer and / or cancer risk. In the tumor-bearing breasts, we sampled adipose tissues adjacent to or distant from the tumor. Parameters studied include: adipocytes size and density; immune cells infiltration, vascularization, functional excretion and gene expression. Adipose tissues from tumor-bearing breasts whether adjacent to or distant from the tumor, did not differ from each other by any of these parameters. By contrast, when compared to adipose tissues from tumor-free breasts, tissues from tumor-bearing breasts displayed functional characteristics pointing to some sort of \\"activation\\". They have the capacity to excrete twice as much of interleukin 8 (p=0.001) and they differentially express a set of around 200 genes, at a threshold of p-value 0.001, of which many belong to inflammation mediated by chemokine and cytokine signaling and integrin signaling pathways. The presence of mast cells appears as a strong predictor of IL-8 secretion capacity (Log2 scale p = 0.002). Therefore, breast fat tissues from breast cancer patients have distinct functional and expression profiles. Although a dialogue effect with the tumor cannot be ruled out, it is also possible that this status is individually defined thus determining the constitutive permissiveness of the tissue for the development of cancer. The activation of pathways that was observed could potentially be translated into biomarkers or therapeutic targets. This transcriptomic analysis has been performed on two types of samples at short and long distances from the tumour in comparison with samples from normal tissues on Illumina beadarrays.
2020-10-05 | E-MTAB-8638 | biostudies-arrayexpress
Project description:High mammographic density (MD) is associated with a 4-6 times increase in breast cancer risk. MD often decreases over time, but little is known about the corresponding biological mechanisms. We obtained biopsies from breasts of healthy women at two different time points years apart. After RNA isolation, Agilent Sureprint G3 Human Gene Expression 8x60K microarrays were performed. Mammographic density was calculated based on mammograms. We explored associations between clinical parameters, MD and gene expression and performed microenvironment tissue subtyping. Gene expression data from previous biopsies are deposited separately.
2019-01-01 | E-MTAB-5885 | biostudies-arrayexpress
Project description:There exists a common deletion polymorphism on the genetic loci of APOBEC3B and this polymorphism exist in ~37% of East Asians and ~7% of Europeans. Germline APOBEC3B deletion has bee27233495n shown to confer modest risk to breast cancer in both East Asian women and women of European descent We performed expression profiling by array to investigate the significantly differentially expressed genes and enriched gene sets in APOBEC3B-null vs. APOBEC3B breast cancers
2016-09-18 | GSE73540 | GEO
Project description:<p>The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center [<a href="www.komentissuebank.iu.edu" target="_blank">www.komentissuebank.iu.edu</a>] (KTB) was established expressly for the prospective collection of normal, healthy breast tissue from volunteer donors. Blood is also obtained from donors at the time of donation and is processed for serum, plasma and peripheral blood leukocyte DNA. Specimens are annotated and data includes age, race, ethnicity, personal health history, family cancer history, medication usage at the time of donation, and breast cancer risk factors.</p> <p>Premenopausal donors to the KTB were identified by a query of the Bank's database. Hematoxylin and eosin stained sections of the formalin-fixed paraffin-embedded tissue of the identified donors were reviewed and tissue was graded on the basis of the abundance of epithelium within the section. Only tissue containing abundant epithelium was considered for this study. Based on dates, the specimens of nine women in the follicular phase of the menstrual cycle and five in the luteal phase were chosen. Six donors using hormonal contraception at the time of donation were also included. Whole blood obtained from 19 of the 20 donors at the time of tissue donation was available and it was processed for serum. Estradiol, estriol, luteinizing hormone and progesterone concentrations were determined by the Indiana University Health Pathology Laboratory using a Beckman Unicel DxI 800 Immunoassay System. The phase of the menstrual cycle was verified by serum progesterone concentration. The epithelium of these 20 specimens was microdissected from multiple 8 micron frozen tissue sections. Total RNA extracted from the tissue was subsequently depleted of rRNA via locked nucleic acid probes. This enabled profiling of both poly-A and non-poly-A RNA species. Barcoded cDNA libraries from the 20 normal breast epithelia were prepared and sequenced on an Applied Biosystems (AB) SOLiD3 or SOLiD 4 platform. RNA-seq reads for each sample were then mapped to the human genome (hg19) using the LifeScope software version 2.5.1 (Life Technologies, Foster City, CA) and BAM (Binary Alignment/Map) files generated. Read counts for each gene were derived from the output BAM files using the RefSeq database (UCSC Genome Brower) as the gene model.</p>
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