Project description:Circulating microRNAs (c-miRNAs) have emerged as measurable biomarkers (liquid biopsies) for cancer detection. The goal of our study was to identify novel biomarkers to predict long-term breast cancer risk in cancer-free women. We evaluated the ability of c-miRNAs to identify women most likely to develop breast cancer by profiling miRNA from serum obtained long before diagnosis. 24 breast cancer cases and controls (matched for risk and age) were identified from women enrolled in the High-Risk Breast Program at the UVM Cancer Center. We used Affymetrix miRNA v4 microarrays to interrogate miRNAs (miRBase v20) in the serum of cancer-free women at high-risk for breast cancer. The 24 cases developed breast cancer at least 6 months (average of 3.2 years) and the 24 controls remain cancer-free.
Project description:Breast cancer develops through the accumulation of genomic changes in the ductal epithelia cells of normal breast tissue. A determination of whether gene expression changes in ductal cells is associated with an increased risk for breast cancer is needed. We sought to determine if the global gene expression profiles of ductal cells of women at high risk for breast cancer or with cytologic ductal epithelial atypia differed from those of women at normal risk or without cytologic atypia. We used microarrays to detail the gene expression profile of breast ductal cells associated with normal risk or high risk for sporadic breast cancer and with or without cytologic epithelial atypia. We did not identify any separation of the sample groups (normal risk vs high-risk, or atypia vs nonatypia) according to expression of subgroups of genes.
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.
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.
Project description:This SuperSeries is composed of the SubSeries listed below. Gene expression profiling of continuous or intermittent energy restriction in women at increased risk of breast cancer