SAGES: Structural Analysis of Gene and Protein Expression Signatures Reveal Dynamic Expression of Disordered Proteins in Breast Cancer and Tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227679 | GEO | 2024/03/31
REPOSITORIES: GEO
Similar Datasets
Project description:Chromosomal structural mutations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural mutations, we analyzed a representative sampling of the major types of breast tumor samples for detailed structural mutations using paired-end tag sequencing of long-insert genomic DNA (DNA-PET) with matched transcriptome ascertainment by RNA-seq. Compared with other structural mutations, tandem duplications are enriched around partners of fusion transcripts and demarcate regions of high gene expression. Moreover tandem duplications appear to be early events in tumor evolution by facilitating subsequent downstream amplification and deletion of important adjacent cancer associated genes. In a detailed reconstruction of events in chr17, we found large unpaired-inversions connect a duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently co-amplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in human normal mammary epithelial cells. Finally, using in silico approaches, we determined that genes whose expression in breast tumors are associated with either poor or good clinical prognosis appear clustered together in segments of frequent amplification or deletion, suggesting that structural abnormalities induce the loss or gain of blocks of adjacent genes with oncogenic or growth suppressor function. These analyses suggest that structural mutations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously. RNA sequencing of four primary breast cancer RNA samples (SOLiD, Applied Biosystems).
2014-07-01 | E-GEOD-57914 | biostudies-arrayexpress
Project description:Disordered regions within RNA binding proteins are required to control mRNA decay and protein synthesis. To understand how these disordered regions modulate gene expression, we surveyed regulatory activity across the entire disordered proteome using a high-throughput functional assay. We identified hundreds of regulatory sequences within intrinsically disordered regions and demonstrate how these elements cooperate with core mRNA decay machinery to promote transcript turnover. Coupling high-throughput functional profiling with mutational scanning revealed diverse molecular features, ranging from defined motifs to overall sequence composition, underlying the regulatory effects of disordered peptides. Machine learning analysis implicated aromatic residues in particular contexts as critical determinants of repressor activity, consistent with their roles in forming protein-protein interactions with downstream effectors. Our results define the molecular principles and biochemical mechanisms that govern post-transcriptional gene regulation by disordered regions and exemplify the encoding of diverse yet specific functions in the absence of well-defined structure.
2024-02-02 | GSE254492 | GEO
Project description:Landscape of G-quadruplex DNA structural regions in breast cancer
| PRJNA638648 | ENA
Project description:Chromosomal structural mutations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural mutations, we analyzed a representative sampling of the major types of breast tumor samples for detailed structural mutations using paired-end tag sequencing of long-insert genomic DNA (DNA-PET) with matched transcriptome ascertainment by RNA-seq. Compared with other structural mutations, tandem duplications are enriched around partners of fusion transcripts and demarcate regions of high gene expression. Moreover tandem duplications appear to be early events in tumor evolution by facilitating subsequent downstream amplification and deletion of important adjacent cancer associated genes. In a detailed reconstruction of events in chr17, we found large unpaired-inversions connect a duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently co-amplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in human normal mammary epithelial cells. Finally, using in silico approaches, we determined that genes whose expression in breast tumors are associated with either poor or good clinical prognosis appear clustered together in segments of frequent amplification or deletion, suggesting that structural abnormalities induce the loss or gain of blocks of adjacent genes with oncogenic or growth suppressor function. These analyses suggest that structural mutations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously.
2014-07-01 | GSE57914 | GEO
Project description:Transcriptional profiling was conducted on RNA from 23 breast cancer cell lines to identify genes whose expression level correlates with sensitivity of particular drug Experiment Overall Design: Baseline gene expression profiling was performed using 23 breast cancer cell lines to identify genomic signatures highly correlated with in vitro sensitivity to a particular drug
2008-06-15 | E-GEOD-6569 | biostudies-arrayexpress
Project description:The three-dimensional (3D) organization of the genome within the cell nucleus contributes to cell-specific gene expression in different cell types1. High-throughput 3CM-bM-^@M-^Sderived methods have revealed that the genome is segmented into contiguous topologically associating domains (TADs), which help to orchestrate gene expression changes during differentiation and development2-5. Using ChIP-Seq, Hi-C and 3D modelling techniques, we reveal that TADs regulate the rapid gene expression changes induced by progestin in T47D breast cancer cells. In response to the hormone, TADs maintain their borders and operate as discrete regulatory units in which the majority of the genes are either transcriptionally activated or repressed. Additionally, the epigenetic signatures of the TADs are coordinately modified by hormone in correlation with the transcriptional changes. Hormone-induced changes in gene activity and chromatin remodelling are accompanied by structural changes that are distinct for activated or repressed TADs. Integrative 3D modelling revealed that TADs are structurally expanded if active and compacted if repressed, and that this is accompanied by differential changes in accessibility. We thus propose that TADs function as M-bM-^@M-^\regulonsM-bM-^@M-^] to enable spatially proximal genes to be coordinately transcribed in response to hormones. T47D-MTVL human breast cancer cells were incubated with the progestin R5020 for different times at 37M-BM-:C and prepared for ChIP-Seq or Hi-C according published protocols
2014-10-06 | E-GEOD-53463 | biostudies-arrayexpress
Project description:Human Breast Microbiome Correlates with Prognostic Features and Immunological Signatures in Breast Cancer
| PRJEB43655 | ENA
Project description:Breast cancer accounts for roughly 30% of all cancers in women worldwide, has a 15% death rate, and incidence rates are increasing at a rate of about 0.5% per year. Breast cancer comprises a heterogeneous group of tumor subtypes, whether defined by the histopathology of the primary tumor, the expression pattern of hormone receptors (estrogen and/or progesterone receptors; ER/PR) and epidermal growth factor receptor 2 (HER2), genetic alterations of transcriptomic traits. These patient-to-patient differences (as known as �쁦ntertumoral heterogeneity��, largely affect patient prognosis and treatment options. Alongside intertumoral heterogeneity, many studies reported that breast cancers heterogeneous consisting of many different cells or subclones of which different gene expression profiles within a patient�셲 primary tumor and individual metastases. These differences within the tumor are referred to as intratumor heterogeneity, which is caused by a combination of extrinsic factors from the tumor microenvironment and intrinsic parameters including genetic, epigenetic and transcriptomic traits, ability of proliferation, migration and invasion, cell plasticity, and the extent of stemness. These heterogeneities endow tumors with multiple capabilities and biological characteristics, making them more prone to metastasis, recurrence, and drug resistance. To overcome these facing challenges, understanding the proteome mechanisms behind transcriptome profiling from the aspect of treatment can help to improve resistance to cancer therapy. Recent proteomics technologies based on mass spectrometry enable an unbiased investigation of drug-induced changes in protein abundance and post-translational modifications. Several studies on resistance to chemotherapy have recently published data on mass spectrometry-based chemotherapeutic proteome profiling, which has the potential to discover molecular subtypes and related pathway features that may have been missed in prior transcriptome analyses. Nevertheless, few proteomics studies to date explore three types of drug-specific resistance of breast cancer signatures. In this study, we employed tandem mass tag (TMT) based proteomics technology to process the acquired mass spectrometry data to test the hypothesis that the chemotherapy in breast cancer cells may have distinct protein profiles that may result in their drug properties and new clinical implications. By unraveling the protein signatures across tamoxifen, doxorubicin, and paclitaxel and their relationship between drug-resistant cell lines and normal breast cancer cells, our study advances the understanding of drug-specific resistance and provides potential diagnostic and prognostic markers, as well as testable targets of therapy specific to breast cancer resistant cells.
2022-04-04 | PXD030881 | Pride
Project description:Recently, expression profiling of breast carcinomas has revealed gene signatures that predict clinical outcome, and discerned prognostically relevant breast cancer subtypes. Measurement of the degree of genomic instability provides a very similar stratification of prognostic groups. We therefore hypothesized that these features are linked. We used gene expression profiling of 48 breast cancer specimens that profoundly differed in their degree of genomic instability and identified a set of 12 genes that defines the two groups. The biological and prognostic significance of this gene set was established through survival prediction in published datasets from patients with breast cancer. Of note, the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets predicted genomic instability in our samples. This remarkable congruence suggests a biological dependency of poor-prognosis gene signatures, breast cancer subtypes, genomic instability, and clinical outcome. Keywords: disease state analysis 44 samples
2009-11-30 | E-GEOD-11901 | biostudies-arrayexpress
Project description:Cancer genomes are characterized by accumulation of small-scale somatic mutations as well as large-scale chromosomal deletions, amplifications, and complex structural rearrangements. This characteristic is at least partially dependent on the ability of cancer cells to undergo recurrent chromosome breakage. In order to address to what extent chromosomal structural rearrangement breakpoints correlate with recurrent DNA double strand breaks (DSBs), we simultaneously mapped chromosome structural variation breakpoints by whole genome DNA-seq and spontaneous DSB formation by Break-seq in the breast cancer cell line MCF-7 and a non-cancer control cell line MCF-10A. We identified concurrent DSBs and structural variation breakpoints almost exclusively in the pericentromeric region of chromosome 16q in MCF-7 cells. We fine-tuned the identification of copy number variation breakpoints on 16q. In addition, we detected recurrent DSBs that occurred in both MCF-7 and MCF-10A. We propose a model for DSB-driven chromosome rearrangements that led to the translocation of 16q, likely with 10q, and the eventual 16q loss that does not involve the pericentromere of 16q. We present evidence from RNA-seq data that select genes, including SHCBP1, ORC6 and MYLK3, which are immediately downstream from the 16q pericentromere show heightened expression in MCF-7 cell line compared to the control. Data published by The Cancer Genome Atlas showed that all three genes have increased expression in breast tumor samples. We suggest that these genes are potential oncogenes for breast cancer progression. The search for tumor suppressor loss that accompanies the 16q loss ought to be augmented by the identification of potential oncogenes that gained expression during chromosomal rearrangements.
2022-07-12 | GSE207714 | GEO