Epigenetic field cancerization in breast cancer using subject-matched tumor, ipsilateral-normal, and contralateral-normal tissues
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA553244 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Emerging work has demonstrated that histologically normal (non-tumor) tissue adjacent to breast tumor tissue shows evidence of molecular alterations related to tumorigenesis, referred to as field cancerization effects. Although changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumor DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumor. Matched tumor, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select breast epithelial cells from normal tissues, and neoplastic cells from tumor specimens for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array. We identified substantially more CpG loci that were differentially methylated between contralateral-normal breast and tumor tissue (63,271 CpG loci q < 0.01), than between ipsilateral-normal tissue and tumor (38,346 CpG loci q < 0.01). In addition, we identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p < 0.01). Hypomethylated loci in ipsilateral normal relative to contralateral were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3. Hypermethylated loci in ipsilateral-normal relative to contralateral-normal tissue were significantly enriched for CpG island shore regions.
2020-07-10 | GSE133985 | GEO
Project description:The retinal projection neurons, retinal ganglion cells (RGCs), can be categorized into distinct morphological and functional subtypes and by the laterality of their projections. Here, we used a new method for purifying the sparse population of ipsilaterally projecting RGCs in mouse retina from their contralaterally-projecting counterparts during embryonic development through rapid retrograde labeling followed by fluorescence-activated cell sorting (FACS). Through microarray analysis, we have uncovered the distinct molecular signatures that define and distinguish ipsilateral and contralateral RGCs during the critical period of axonal outgrowth and decussation, with over three hundred genes differentially experienced within these two cell populations. Amongst the genes upregulated in ipsilateral RGCs are many that are known to be expresed in progenitors cells and mark “immaturity," including Math5 (Atoh7), Sox2, and cyclin D2. Many of these differentially regulated genes were subsequently validated via in vivo expression analysis. Thus, the molecular signatures of ipsilateral and contralateral RGCs and the mechanisms that regulate their differentiation are more diverse than previously expected.
2016-12-05 | GSE83461 | GEO
Project description:This study relates to embryo-maternal interaction. The aim was to compare the transcriptome and ability of the ipsilateral and contralateral uterine horns to support preimplantation conceptus survival and growth to Day 14. Although differences in gene expression exist between the endometrium of uterine horns ipsilateral and contralateral to the CL in cattle, they do not impact conceptus survival or length between Days 7 and 14.
2018-08-15 | GSE118507 | GEO
Project description:The spinal cord receives inputs from the cortex via corticospinal neurons (CSNs). While predominantly a contralateral projection, a less-investigated minority of its axons terminate in the ipsilateral spinal cord. We analyzed the spatial and molecular properties of these ipsilateral axons and their post-synaptic targets in mice and found they project primarily to the ventral horn, including directly to motor neurons. Barcode-based reconstruction of the ipsilateral axons revealed a class of primarily bilaterally-projecting CSNs with a distinct cortical distribution. The molecular properties of these ipsilaterally-projecting CSNs (IP-CSNs) are strikingly similar to the previously described molecular signature of embryonic-like regenerating CSNs. Finally, we show that IP-CSNs are spontaneously regenerative after spinal cord injury. The discovery of a class of spontaneously regenerative CSNs may prove valuable to the study of spinal cord injury. Additionally, this work suggests that the retention of juvenile-like characteristics may be a widespread phenomenon in adult nervous systems. This TRAP sequencing data was used to determine the molecular similarity to regenerating and embryonic CSNs.
2024-09-23 | GSE277676 | GEO
Project description:Viral TRAP RNAseq Data from Ipsilateral and Contralateral Corticospinal Neurons in Mouse
| PRJNA1163333 | ENA
Project description:Cancer local recurrence increases the mortality of patients, and might be caused by field cancerization, a pre-malignant alteration of normal epithelial cells. It has been suggested that cancer-derived small extracellular vesicles (CDEs) may contribute to field cancerization, but the underlying mechanisms remain poorly understood. In this study, we aim to identify the key regulatory factors within recipient cells under the instigation of CDEs. In vitro experiments were performed to demonstrate that CDEs promote the expression of CREPT in normal epithelial cells. TMT-based quantitative mass spectrometry was employed to investigate the proteomic differences between normal cells and tumor cells. Loss-of-function approaches by CRISPR-Cas9 system were used to assess the role of CREPT in CDEs-induced field cancerization. RNA-seq was performed to explore the genes regulated by CREPT during field cancerization. CDEs promote field cancerization by inducing the expression of CREPT in non-malignant epithelial cells through activating the ERK signaling pathway. Intriguingly, CDEs failed to induce field cancerization when CREPT was deleted, highlighting the importance of CREPT. Transcriptomic analyses revealed that CDEs elicited inflammatory responses, primarily through activation of the TNF signaling pathway. CREPT, in turn, regulates the transduction of downstream signals of TNF by modulating the expression of TNFR2 and PI3K, thereby promoting inflammation-to-cancer transition. CREPT not only serves as a biomarker for field cancerization, but also emerges as a target for preventing the cancer local recurrence.
2023-12-10 | GSE249383 | GEO
Project description:Previous work has shown that lung tumors and normal-appearing adjacent lung tissues share specific abnormalities that may be highly pertinent to the pathogenesis of lung cancer. However, the global and molecular adjacent airway field cancerization in non-small cell lung cancer (NSCLC) has not been characterized before. We sought to understand the transcriptomic architecture of the adjacent airway field canerization, in conjunction with tumors, to gain additional insights into the lung cancer biology and oncogenesis. We analyzed the transcriptome, using the Affymetrix Human Gene 1.0 ST platform, of matched NSCLC tumors, multiple normal airway epithelia with differential distance from the tumors as well as uninvolved normal lung tissues. We analyzed the airway field cancerization transcritpome to determine global differentially expressed cancerization profiles in adjacent airways as well as airway profiles that may be modulated by distance from tumors.
2014-03-04 | E-GEOD-44077 | biostudies-arrayexpress
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients.
2015-01-06 | GSE54541 | GEO
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients.
2015-01-06 | GSE54495 | GEO
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients. We collected peripheral airway brushings from the contral-lateral lung of the tumor from cancer patients (n=17) and smoker controls (n=13); Total RNA were obtained from the peripheral airway epithelium.
2015-01-06 | E-GEOD-54541 | biostudies-arrayexpress