Similar Datasets
Project description:Genome wide H3K27ac CHIP sequencing was performed in the ER positive breast cancer cell line MCF7 cultured in serine-free media for 24h, with or without supplementation with 2 mM glycerol triacetate.
2023-08-01 | GSE222341 | GEO
Project description:We cultured the ER negative breast cancer cell line MDA-MB-231 and the ER positive breast cancer cell line MCF7 in serine-free media for 24h. RNA was extracted from the cells and submitted for RNA sequencing.
2023-08-01 | GSE222313 | GEO
Project description:While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events.Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample.Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is surprisingly homogeneous, defining two main subtypes which strongly correlate with luminal-A/B subtype status. In particular, we identify WNT and BMP signalling as key epigenetically deregulated tumour suppressor pathways in luminal ER+ breast cancer, with increased deregulation seen in luminal-B breast cancer.
| S-EPMC4673726 | biostudies-other
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-09-22 | GSE171412 | GEO
Project description:Transcriptomic analysis of fresh breast cancer tissue versus normal tissues. The Study comprising 45 Saudi-Arabian subjects was designed to take advantage of transcriptomics to prospectively explore the roles of lifestyle and genetic susceptibility in the occurrence of breast cancer. Total RNA isolated from 45 surgically resected breast cancer tissues and 8 healthy breast tissues (3 from Affymetrix) and purified, labeled, and hybridized to Affymetrix Human Gene 1.0 ST Array.
| S-ECPF-GEOD-36295 | biostudies-other
Project description:Cancer-specific changes in DNA methylation can alter genetic stability, genomic structure, and gene expression. Promoter CpG island methylation can result in transcriptional silencing and plays an important role in the oncogenic process. We used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Here, we describe the identification of novel groups of breast tumors characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating the existence of a breast-CpG island methylator phenotype (B-CIMP). B-CIMP imparts a distinct epigenomic profile and is a strong determinant of metastatic potential. Gene Expression Samples (GSM647057-GSM647077): Twenty-one breast cancer primary samples were analyzed. There are 10 CIMP positive and 11 CIMP negative samples. Methylation Profiling Samples (GSM651372-GSM651410): Thirty-nine breast cancer primary samples were analyzed. There are 17 CIMP positive and 22 CIMP negative samples.
| S-ECPF-GEOD-26349 | biostudies-other
Project description:Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here we combined single-cell multi-omics, transcriptomics and methylomics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~3,800 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the phenotypic traits of the subclasses, and the study of additional unstratified KC entities uncovered distinct clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis.
| S-SCDT-10_15252-MSB_202211073 | biostudies-other
Project description:Patients diagnosed with breast cancer were recruited to an important trial, the Tamoxifen Window Trial, in two series, series A during 1988-1989 and series B during 1989-1990. Some patients received tamoxifen for short windows. Clinical samples (biopsies) for this trial were collected before and after treatment. These biopsies were available as formalin-fixed paraffin-embedded (FFPE) tissue blocks. Responding patients and non-responding patients were determined by the change in the Ki67 scores. Responding patients were identified as those that had demonstrated a reduction in their Ki67 scores, and non-responding patients were identified as those in which Ki67 had not changed or had increased. The change in the percentage of Ki67 positive tumour cells was obtained by comparing the pre-treatment and post-treatment scores and calculating the difference in the scores. Laser capture microdissection (LCM) was utilised to microdissect the epithelial and stromal cells from the post-treatment breast cancer FFPE tissue sections of responding and non-responding patients. Samples obtained following LCM underwent RNA extraction and were subsequently used for gene expression profiling. Post-treatment samples from three responding patients (A29, B42, B61) and three non-responding patients (A15, A19, B59) were identified as suitable for this study and underwent LCM. Samples were analysed using Affymetrix GeneChip® Human Exon 1.0 ST array. No technical replicates were performed. The stromal compartments collected from post-treatment samples of patients B59 and B61 failed to generate the appropriate yield of cDNA following two rounds of amplification and consequently were excluded from further analysis. Array hybridisation of samples were performed in 3 separate batches.
| S-ECPF-GEOD-58598 | biostudies-other
Project description:The purpose of this study was to examine whether at-diagnosis smoking and postdiagnosis changes in smoking within five years after breast cancer were associated with long-term all-cause and breast cancer-specific mortality. A population-based cohort of 1508 women diagnosed with first primary in situ or invasive breast cancer in 1996 to 1997 were interviewed shortly after diagnosis and again approximately five years later to assess smoking history. Participants were followed for vital status through December 31, 2014. After 18+ years of follow-up, 597 deaths were identified, 237 of which were breast cancer related. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with never smokers, risk of all-cause mortality was elevated among the 19% of at-diagnosis smokers (HR=1.69, 95% CI=1.36 to 2.11), those who smoked 20 or more cigarettes per day (HR=1.85, 95% CI=1.42 to 2.40), women who had smoked for 30 or more years (HR=1.62, 95% CI=1.28 to 2.05), and women who had smoked 30 or more pack-years (HR=1.82, 95% CI=1.39 to 2.37). Risk of all-cause mortality was further increased among the 8% of women who were at-/post-diagnosis smokers (HR=2.30, 95% CI=1.56 to 3.39) but was attenuated among the 11% women who quit smoking after diagnosis (HR=1.83, 95% CI=1.32 to 2.52). Compared with never smokers, breast cancer-specific mortality risk was elevated 60% (HR=1.60, 95% CI=0.79 to 3.23) among at-/postdiagnosis current smokers, but the confidence interval included the null value and elevated 175% (HR=2.75, 95% CI=1.26 to 5.99) when we considered postdiagnosis cumulative pack-years. Conclusions: Smoking negatively impacts long-term survival after breast cancer. Postdiagnosis cessation of smoking may reduce the risk of all-cause mortality. Breast cancer survivors may benefit from aggressive smoking cessation programs starting as early as the time of diagnosis.
| S-EPMC5875926 | biostudies-literature
Project description:Cancer cells acquire distinct metabolic adaptations to survive stress associated with tumour growth and to satisfy the anabolic demands of proliferation. The tumour suppressor protein p53 (also known as TP53) influences a range of cellular metabolic processes, including glycolysis, oxidative phosphorylation, glutaminolysis and anti-oxidant response. In contrast to its role in promoting apoptosis during DNA-damaging stress, p53 can promote cell survival during metabolic stress, a function that may contribute not only to tumour suppression but also to non-cancer-associated functions of p53. Here we show that human cancer cells rapidly use exogenous serine and that serine deprivation triggered activation of the serine synthesis pathway and rapidly suppressed aerobic glycolysis, resulting in an increased flux to the tricarboxylic acid cycle. Transient p53-p21 (also known as CDKN1A) activation and cell-cycle arrest promoted cell survival by efficiently channelling depleted serine stores to glutathione synthesis, thus preserving cellular anti-oxidant capacity. Cells lacking p53 failed to complete the response to serine depletion, resulting in oxidative stress, reduced viability and severely impaired proliferation. The role of p53 in supporting cancer cell proliferation under serine starvation was translated to an in vivo model, indicating that serine depletion has a potential role in the treatment of p53-deficient tumours.
| S-EPMC6485472 | biostudies-literature