Whole methylome analysis of breast tissues prior to breast cancer diagnosis [methyl-capture]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE166045 | GEO | 2021/09/30
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 Comprehensive Cancer Center (KTB) is the only repository of normal breast tissues donated by healthy women. Here, we examined the transcriptome profiling of normal breasts from 190 healthy women, including 62 African Americans, 11 Asians, and 109 Caucasians. Correlation analysis between geen expression and risk factors for breast cancer (such as smoking, BMI, age, racial background) was performed.
2023-09-12 | GSE205725 | 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: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: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:The underlying biology through which established breast cancer risk factors contribute to disease risk is not well characterized. One key risk factor for breast cancer is age, and age-related DNA methylation alterations may contribute to increased risk of disease. Here we assessed normal breast tissues and tested the relation of DNA methylation with known breast cancer risk factors. Cancer-free women donated breast tissue biopsy specimens through the Susan G. Komen Foundation and provided detailed risk factor data (n=100). Bisulfite modified DNA was profiled for DNA methylation genome-wide using the Infinium 450K DNA methylation array. We tested the relation of known breast cancer risk factors such as age, BMI, parity, and family history of disease with DNA methylation adjusted for variation in cell type proportions using a novel cellular mixture deconvolution algorithm. We identified 787 CpGs that exhibited significant (FDR adjusted, q-value < 0.01) differential DNA methylation associated with subject age, but not with other breast cancer risk factors. We observed an enrichment among the risk factor-related CpGs for Polycomb group target genes (Fisher’s Exact test, P = 1.74E-06), and breast myoepithelial cell enhancer regions (H3K4me1; Fisher’s Exact test, P = 7.1E-20). We validated our risk factor-related findings in two independent populations of normal breast tissue (n=18 and n=97). In addition, age-related CpGs were further deregulated in both pre-invasive (DCIS, n=40) and invasive breast cancers (TCGA, n=731). Overall, our results suggest that the breast cancer risk factor age contributes to epigenetic dysregulation in normal breast tissue that exhibit progressive changes in cancer.
2017-06-20 | GSE88883 | GEO
Project description:In addition to the accumulation of pro-oncogenic mutations in the epithelial cells, the tumorigenic process involves the dysregulation of the interactions between the epithelial cells and their microenvironment, as well as alterations within the microenvironment itself. Therefore, investigating the causes of the loss of the normal tissue homeostasis in the earliest stages of breast cancer carcinogenesis is the necessary underpinning of an effective breast cancer prevention strategy. In order to comprehensively capture the transcriptomic alterations occurring in the breast in a precancerous stage, we examined a unique resource present in our institute including breast tissue biopsies donated by women two to six years prior to the clinical manifestation of breast cancer (labeled “susceptible normal tissue”) as well as specimens from healthy women. Donors in the two cohorts were at a premenopausal status and were matched according to age, racial background and menstrual phase. Both the susceptible and healthy breast tissues appear histologically normal. Upon microdissection of the three breast tissue compartments including epithelial, stromal and adipose tissue, transcriptomic analysis was performed. Upregulation of genes involved in lipid metabolism and fatty acid transport was observed also in the susceptible stroma and adipose tissue compartments, respectively.
2019-12-12 | GSE141828 | GEO
Project description:miRNA expression from breast tumor tissue obtained from two groups of breast cancer (BC) patients: one group formed by women younger than 36 years and the other group by women older than 65 years. We selected breast tumor tissue samples from 21 women under 36 years old and 12 women above 65 years old, without BRCA mutation and without metastases. We selected a pool of samples in which all the subtypes were representated, in young patients as well as in older patients, to avoid expression biass. We add three samples from breast tissue of cancer-free women to minimize the age-related expression biass. Our aim was to compare miRNA expression between young women and older women, considering normal tissue as a reference.
2014-09-12 | E-GEOD-48088 | 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: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