The goal of our study is to build an integrated transcriptome landscape model for HER2 positive breast tumors and identify the crucial signaling pathways associated with HER2 tumors. Genomic features include, 685 genes that were differentially expressed only in HER2-positive tumors, 102 genes that were alternatively spliced in a pattern that is unique to HER2-positive tumors, and 303 genes that expressed single nucleotide sequence variants (eSNVs) that were unique to HER2-positive tumors. Network analysis was performed to integrate the genomic features into a transcriptome landscape model that identified 12 highly interconnected cellular processes that appear to be critical to the establishment and maintenance of HER2-positive tumors. We observed that integrin signaling was linked to lapatinib sensitivity in vitro and strongly associated with risk of relapse in the NCCTG N9831 adjuvant trastuzumab clinical trial dataset. Overall design: We analyzed RNA-seq data from a survey panel consisting of 8 benign breast lesions, 8 ER+, 8 triple negative, and 8 HER2-positive primary breast tumors to identify genomic features that were uniquely associated with HER2-positive tumors
An integrated model of the transcriptome of HER2-positive breast cancer.
Specimen part, Subject
View SamplesAnaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. While ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22-rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22-rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced representation bisulfate sequencing and DNA methylation arrays. Pharmacologic DNA demethylation in ALCL cells recapitulated the overexpression of CTAs and other DUSP22 signature genes. Additionally, DUSP22-rearranged ALCLs minimally expressed PD-L1 compared to other ALCLs, but showed high expression of the costimulatory gene CD58 and HLA class II. Taken together, these findings indicate that DUSP22 rearrangements define a molecularly distinct subgroup of ALCLs and that immunogenic cues related to antigenicity, costimulatory molecule expression, and inactivity of the PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. More aggressive ALCLs might be pharmacologically reprogrammed to a DUSP22-like, immunogenic molecular signature through the use of demethylating agents and/or immune checkpoint inhibitors.
Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with <i>DUSP22</i> rearrangements.
No sample metadata fields
View SamplesTIMP-4 overexpression increases tumor burden in mice, promotes progenitor cell phenotype and sensitizes cells to apoptosis, by relying on NFkB signaling
Tissue inhibitor of metalloproteinases-4 (TIMP-4) regulates stemness in cervical cancer cells.
Specimen part, Cell line
View SamplesWe constructed a polycistronic lentiviral vector to overexpress 3 germ cell specific genes (Stella, Oct4 and Nanos2) in mouse embryonic fibroblast (MEFs) and evaluated the transcriptome portrait in partially reprogrammed cells.We sequenced RNA samples from bulk cell population of two biological duplicates of MEF-GFP (control) and MEF-SON (overexpressed) 21 days post infection. Differential expression analysis of 50 M pair-end read per samples showed overexpression of neurogenesis, blood vessel and proliferation related genes and downregulation of chondroitin sulphate metabolic process, nitric oxide production and innate immune response genes. Overall design: Examination of whole transcriptome following concurrent overexpression of Stella, Oct4 and Nanos2 in MEFs.
Suppression of dsRNA response genes and innate immunity following Oct4, Stella, and Nanos2 overexpression in mouse embryonic fibroblasts.
Specimen part, Cell line, Subject
View SamplesZebrafish (Danio rerio) gutGFP transgenic embryos [Tg(XlEef1a1:GFP)s854] were collected at 4 time points: 2 days post fertilization (dpf), 3, dpf, 4 dpf, 6 dpf. Embryos were dissociated into single cells and sorted by FACS based on GFP expression.
FACS-assisted microarray profiling implicates novel genes and pathways in zebrafish gastrointestinal tract development.
Age
View SamplesChemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis, a dose-limiting side effect for effective cancer treatment.
Microarray analyses of oral punch biopsies from acute myeloid leukemia (AML) patients treated with chemotherapy.
No sample metadata fields
View SamplesTwenty eight genes in PAO1 persister cells were consistently induced by treatment with 1 ug/mL BF8 for 1 h.
Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one.
Specimen part, Treatment
View SamplesOur earlier study demonstrated that when CFSE-labeled LCMV-or Pichinde virus-immune spleen leukocytes were transferred into T cell-deficient hosts, the bona fide virus-specific memory cells underwent relatively limited cell division and were substantially diluted in frequency by other more extensively proliferating cells originating from that donor cell population. We questioned how the slowly dividing population, which contained bona fide memory cells, differed from the rapidly dividing cells, which contained memory-like cells. As a preliminary screen we performed a comparative genome-wide microarray analysis of genes expressed on sorted rapidly proliferating (CFSE-low) and slowly proliferating (CFSE-high) CD8 cell populations
Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation.
Age, Specimen part
View SamplesA data set of normal epithelium, serous ovarian surface epithelial-stromal tumors (benign and type II malignancies), stroma distal to tumor, and stroma adjacent to tumor (50 samples total). Additional cel files are included which represent replicate sampling from patients, and cel files that failed quality control but may be bioinformatically interesting. Additional replicate or failed cel files were not included in the final analysis (and so these samples were not included in the matrix).
Dysregulation of AKT3 along with a small panel of mRNAs stratifies high-grade serous ovarian cancer from both normal epithelia and benign tumor tissues.
Specimen part, Subject
View SamplesBipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex and orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls.
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
Sex, Age, Disease
View Samples