Ontology highlight
ABSTRACT:
PROVIDER: PRJNA398167 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5930975.fastq.gz | Fastqsanger.gz | |||
| SRR5930975_1.fastq.gz | Fastqsanger.gz | |||
| SRR5930975_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
Similar Datasets
Project description:Elucidating the progression mechanism from ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive ductal carcinoma (IDC), remains a critical challenge in oncology. Metabolic profiling of lesions with differential invasiveness may help reveal key drivers underlying DCIS progression. This study employed mass spectrometry imaging to delineate the small-molecule metabolic profiles of DCIS, DCIS with synchronous IDC, and IDC lesions. Key metabolic alterations driving DCIS-to-IDC progression were identified, including elevated fatty acid biosynthesis in tumor tissues. Comparative analyses revealed that IDC exhibited significantly higher accumulation of polyunsaturated fatty acids (PUFAs) than DCIS (P<0.05), consistent with immunohistochemical validation showing upregulated fatty acid desaturase 2 expression in IDC. DCIS lesions predominantly accumulated phosphatidylinositols with saturated/monounsaturated acyl chains, while IDC exhibited a marked enrichment of phosphatidylinositols with PUFA (P<0.01). Furthermore, IDC showed significantly reduced levels of antioxidant molecules (taurine, ascorbic acid, glutathione) and the detoxification enzyme glutathione S-transferase mu 2 compared to DCIS (P<0.05), indicating dysregulation of redox homeostasis. Strikingly, DCIS with synchronous IDC displayed metabolic signatures closely aligned with IDC, suggesting its role as a transitional state during malignant progression. These findings indicate that DCIS malignant progression exhibits metabolic dependency on PUFAs/phosphatidylinositols with PUFA and depletion of antioxidants. Therapeutic targeting of PUFA biosynthesis or redox homeostasis regulators may offer novel translational approaches for tracking and intercepting DCIS progression.
2025-03-26 | GSE292487 | GEO
Project description:Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma (IDC). Annotation of the genetic differences between the two lesions may assist in the identification of genes that promote the invasive phenotype. Matched IDC and DCIS showed highly similar copy number profiles (average of 83% of the genome shared) indicating a common clonal orgin although there is evidence that the DCIS continues to evolve in parallel with the co-existing IDC. Four chromosomal regions of loss (3q, 6q, 8p and 11q) and four regions of gain (5q, 16p, 19q and 20) were recurrently affected in IDC but not in DCIS. CCND1 and MYC showed increased amplitude of gain in IDC. One region of loss (17p11.2) was specific to DCIS. 21 cases of synchronous DCIS and IDC were microdissected from FFPE tissue and analysed by molecular inversion probe (MIP) copy number arrays. The arrays were early release OncoScan arrays and the data in this submission are CN values for the ~300,000 probes common to two batches performed. Raw data is retained by Affymetrix.
2012-09-04 | E-GEOD-31892 | biostudies-arrayexpress
Project description:DCIS is a non-invasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer while others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor intrinsic subtypes, proliferative, immune scores and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immune suppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly ncRNA and methylation profiles reproduce changes observed post-invasion. Among the most significant findings we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and specific SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a pre-invasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. DNA from 24 out of 30 (80%) HG-DCIS samples and 5 normal breast organoids (total 29 samples) were subjected to reduced representation bisulfite sequencing analysis (RRBS) by using Illumina HiSeq2000 platform. Please note that description of samples employed for the NGS analyses including age, race, ER/PR immunohistochemistry results, ITIL/STIL scores and PAM50 classification is provided the 'Supplementary Data1_Samples data.xlsx' (available on Superseries record)
2015-07-25 | E-GEOD-69993 | biostudies-arrayexpress
Project description:Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Its biological features, particularly its intratumoral heterogeneity, remain obscure. Moreover, mechanism of lymph node metastasis is unclear. To address this deficiency, we performed single-cell transcriptome profiling of DCIS, invasive ductal carcinoma (IDC) and lymph node metastasis. Single-cell transcriptome analysis revealed that breast cancer exhibits intratumoral heterogeneity at the transcriptional level, defining specific functions, and that DCIS has similar heterogeneity to IDC.
2022-08-02 | GSE195861 | GEO
Project description:Synchronous ductal carcinoma in situ single cell DNA sequencing
| PRJNA397565 | ENA
Project description:Tandem DCIS/IDC are defined as ductal carcicnoma in situ (DCIS) lesions that have concurrent invasive ductal carcinoma (IDC) within the same breast. These are identified radiologically by an area of clustered microcalcifications adjacent to (contiguous with) an invasive mass. Our radiologist (Dr. William P. Smith) has provided us with biopsy cores from each region. One core from each region (DCIS and IDC) has bas been collected and subjected to RNA sequencing for our studies to compare changes from DCIS to IDC in each individual patient. 6 pairs of DCIS-IDC samples were collected, and analysed by RNA sequencing
2015-02-26 | E-GEOD-66301 | biostudies-arrayexpress
Project description:We attempted to identify alterations in gene expression that occur during the progression from normal breast to ductal carcinoma in situ (DCIS) with the aim to elucidate significant genes and pathways underlying the premalignant transformation. To determine the expression changes that are common to multiple DCIS models (MCF10.DCIS, SUM102 and SUM225) and normal mammary epithelial cells (MCF10A), we grew the cells in three dimensional overlay culture with reconstituted basement membrane and used the extracted RNA for 76 cycles of deep sequencing (mRNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of mRNA-Seq results showed 295 consistently differentially expressed transcripts in DCIS models as compared to MCF10A. These differentially expressed genes are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFM-CM-^_ signaling. Many differentially expressed transcripts in DCIS were found to be involved in cell-cell signaling, cell-cell adhesion and cell proliferation. We further investigated ALDH5A1 gene that encodes for the enzyme, aldehyde dehydrogenase 5A1, which is involved in glutamate metabolism. Further, inhibition of ALDH5A1 with different pharmacological drugs resulted in significant inhibition of cell growth and proliferation in the DCIS models. Four cell lines examined: normal mammary epithelial cell line (one sample) and three ductal carcinoma in situ cell lines (three samples). Each sample has two duplicates
2012-03-28 | E-GEOD-36863 | biostudies-arrayexpress
Project description:We attempted to identify alterations in gene expression that occur during the progression from normal breast to ductal carcinoma in situ (DCIS) with the aim to elucidate significant genes and pathways underlying the premalignant transformation. To determine the expression changes that are common to multiple DCIS models (MCF10.DCIS, SUM102 and SUM225) and normal mammary epithelial cells (MCF10A), we grew the cells in three dimensional overlay culture with reconstituted basement membrane and used the extracted RNA for 76 cycles of deep sequencing (mRNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of mRNA-Seq results showed 295 consistently differentially expressed transcripts in DCIS models as compared to MCF10A. These differentially expressed genes are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFß signaling. Many differentially expressed transcripts in DCIS were found to be involved in cell-cell signaling, cell-cell adhesion and cell proliferation. We further investigated ALDH5A1 gene that encodes for the enzyme, aldehyde dehydrogenase 5A1, which is involved in glutamate metabolism. Further, inhibition of ALDH5A1 with different pharmacological drugs resulted in significant inhibition of cell growth and proliferation in the DCIS models.
2012-03-29 | GSE36863 | GEO
Project description:cDNA aCGH study of pure DCIS (breast duct carcinoma in situ) without invasive tumor, DCIS associated with IDC (breast invasive duct carcinoma) and its IDC component 23 patients: 6 pure DCIS without invasive cancer and no history of invasive cancer, 17 DCIS associated with IDC. Out of the latter 1 tumor had only enough DCIS (#16) for aCGH and one - IDC (#23) Keywords: Comparative clinical study
2009-02-01 | GSE10197 | GEO
Project description:Tandem DCIS/IDC are defined as ductal carcicnoma in situ (DCIS) lesions that have concurrent invasive ductal carcinoma (IDC) within the same breast. These are identified radiologically by an area of clustered microcalcifications adjacent to (contiguous with) an invasive mass. Our radiologist (Dr. William P. Smith) has provided us with biopsy cores from each region. One core from each region (DCIS and IDC) has bas been collected and subjected to RNA sequencing for our studies to compare changes from DCIS to IDC in each individual patient.
2015-02-26 | GSE66301 | GEO