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GSE49284
Homo sapiens
103 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations within the catalytic domain of the histone methyltransferase (HMT) EZH2 have been identified in subsets of Non-Hodgkin Lymphoma (NHL) patients. These genetic alterations are hypothesized to confer an oncogenic dependency on EZH2 enzymatic activity in these cancers. We previously reported the discovery of a potent, selective, S-adenosyl-methionine-competitive and orally bioavailable small molecule inhibitor of EZH2, EPZ-6438. EPZ-6438 selectively inhibits intracellular lysine 27 of histone H3 (H3K27) methylation in a concentration- and time-dependent manner in both EZH2 wild type and mutant lymphoma cells. Inhibition of H3K27 trimethylation (H3K27Me3) led to selective cell killing of human lymphoma cell lines bearing EZH2 catalytic domain point mutations. Treatment of xenograft-bearing mice with EPZ-6438 leads to dose-dependent tumor growth inhibition and eradication of genetically altered NHL with correlative diminution of H3K27Me3 levels in tumors and selected normal tissues. Mice dosed orally with EPZ-6438 for 28 days remained tumor free for up to 63 day after stopping compound treatment in two EZH2 mutant xenograft models. These data confirm the dependency of mutant NHL on EZH2 activity and portend the utility of EZH2-targeted drugs for the treatment of these genetically defined cancers.
Publication Title
Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cell lines bearing MLL translocations (MV4-11 and MOLM-13) were treated with a potent, selective inhibitor of the DOT1L histone methyl transferase. Treatment of MLL-rearranged cell lines with the DOT1L inhibitor selectively inhibits H3K79 methylation and blocks expression of leukemogenic genes. Here we provide expression profiling data of cells treated with DOT1L inhibitor or vehicle control.
Publication Title
Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Oxidative stress is a common phenomenon and is linked to a wide range of diseases and pathological processes. Tissue-specific variation in redox signaling and cellular responses to oxidative stress may be associated with vulnerability to toxic agents and carcinogenic exposures. In order to provide a basis for tissue-specific difference, we examined the tissue-specific transcriptional features of 101 oxidative stress-associated genes in 10 different tissues and organs of healthy mice under physiological conditions.
Publication Title
Tissue-Specific Profiling of Oxidative Stress-Associated Transcriptome in a Healthy Mouse Model.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 678 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
BACKGROUND: In patients with suspicious pulmonary lesions, bronchoscopy is frequently non-diagnostic. This often results in additional invasive testing, including surgical biopsy, although many patients have benign disease. We sought to validate an airway gene-expression classifier for lung cancer in patients undergoing diagnostic bronchoscopy. METHODS: Two multicenter prospective studies (AEGIS 1 and 2) enrolled 1357 current or former smokers undergoing bronchoscopy for suspected lung cancer. Bronchial epithelial cells were collected from normal appearing mucosa in the mainstem bronchus during bronchoscopy. Patients without a definitive diagnosis from bronchoscopy were followed for 12 months. A gene-expression classifier was used to assess the risk of lung cancer, and its performance was evaluated. RESULTS: A total of 298 patients from AEGIS 1 and 341 from AEGIS 2 met criteria for analysis. Bronchoscopy was non-diagnostic for cancer in 272 of 639 patients (43%; 95%CI, 39-46%). The gene expression classifier correctly identified 431 of 487 patients with cancer (89% sensitivity; 95%CI, 85-91%), and 72 of 152 patients without cancer (47% specificity; 95%CI, 40-55%). The combination of the classifier and bronchoscopy had a sensitivity of 97% (95%CI, 95-98%), which was independent of size, location, stage, and histological subtype of lung cancer. In patients with an intermediate pre-test risk (10-60%) of lung cancer, the NPV of the classifier was 91% (95%CI 75-98%). CONCLUSIONS: In patients with an intermediate risk of lung cancer and a non-diagnostic bronchoscopy, a gene-expression classification of low-risk warrants consideration of a more conservative diagnostic approach that could reduce unnecessary invasive testing in patients with benign disease.
Publication Title
A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 594 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 150 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics. Here we report the identification of 2,576 somatic mutations across approximately 1,800 megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. Additionally, 373 tumors were assayed for copy number alterations via Agilent 244A CGH arrays and 153 breast, lung, and colon samples were assayed for mRNA abundance with Affymetrix HuEx1 Exon Arrays.
Publication Title
Diverse somatic mutation patterns and pathway alterations in human cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 294 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancer, a leading cause of cancer related deaths, is a heterogeneous disease, with little consensus on molecular subclasses and their clinical relevance. We describe four molecular subtypes linked with distinct patterns of molecular alterations, disease progression and prognosis viz. a) Microsatellite Instable: hypermutated intestinal subtype tumors occurring in antrum, best overall prognosis, lower frequency of recurrence (22%), with liver metastasis in 23% of recurred cases b) Mesenchymal-like: diffuse tumors with worst prognosis, a tendency to occur at an earlier age and highest recurrence (63%) with peritoneal seeding in 64% of recurred cases, low frequency of molecular alterations c) TP53-inactive with TP53 loss, presence of focal amplifications and chromosomal instability d) TP53-active marked by EBV infection and PIK3CA mutations. The key molecular mechanisms and associated survival patterns are validated in multiple independent cohorts, to provide a consistent and unified framework for further preclinical and clinical research.
Publication Title
Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 294 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 294 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study is designed to compare and contrast the temporal and spatial changes in bone formation rates and transcriptional profiles in cortical and cancellous bone cell populations enriched by laser capture microdissection (LCM) in ovariectomized rats administered Scl-Ab by subcutaneous injection for up to 26 consecutive weeks, followed by a recovery period of up to 18 weeks.
Publication Title
Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 238 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro.
Publication Title
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples