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SRP055835
Homo sapiens
14 Downloadable Samples
IlluminaHiSeq2000
Description
The therapeutic landscape of melanoma is rapidly changing. While targeted inhibitors yield significant responses, their clinical benefit is often limited by the early onset of drug resistance. This motivates the pursuit to establish more durable clinical responses, by developing combinatorial therapies. But while potential new combinatorial targets steadily increase in numbers, they cannot possibly all be tested in patients. Similarly, while genetically engineered mouse melanoma models have great merit, they do not capture the enormous genetic diversity and heterogeneity typical in human melanoma. Furthermore, whereas in vitro studies have many advantages, they lack the presence of micro-environmental factors, which can have a profound impact on tumor progression and therapy response. This prompted us to develop an in vivo model for human melanoma that allows for studying the dynamics of tumor progression and drug response, with concurrent evaluation and optimization of new treatment regimens. Here, we present a collection of patient-derived xenografts (PDX), derived from BRAFV600E, NRASQ61 or BRAFWT/NRASWT melanoma metastases. The BRAFV600E PDX melanomas were acquired both prior to treatment with the BRAF inhibitor vemurafenib and after resistance had occurred, including six matched pairs. We find that PDX resemble their human donors' melanomas regarding biomarkers, chromosomal aberrations, RNA expression profiles, mutational spectrum and targeted drug resistance patterns. Mutations, previously identified to cause resistance to BRAF inhibitors, are captured in PDX derived from resistant melanomThis melanoma PDX platform represents a comprehensive public resource to study both fundamental and translational aspects of melanoma progression and treatment in a physiologically relevant setting. Overall design: Melanoma samples pre and post Vemurafenib treatment from patient and matching patient derived xenografts (PDX)
Publication Title
XenofilteR: computational deconvolution of mouse and human reads in tumor xenograft sequence data.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
The therapeutic landscape of melanoma is rapidly changing. While targeted inhibitors yield significant responses, their clinical benefit is often limited by the early onset of drug resistance. This motivates the pursuit to establish more durable clinical responses, by developing combinatorial therapies. But while potential new combinatorial targets steadily increase in numbers, they cannot possibly all be tested in patients. Similarly, while genetically engineered mouse melanoma models have great merit, they do not capture the enormous genetic diversity and heterogeneity typical in human melanoma. Furthermore, whereas in vitro studies have many advantages, they lack the presence of micro-environmental factors, which can have a profound impact on tumor progression and therapy response. This prompted us to develop an in vivo model for human melanoma that allows for studying the dynamics of tumor progression and drug response, with concurrent evaluation and optimization of new treatment regimens. Here, we present a collection of patient-derived xenografts (PDX), derived from BRAFV600E, NRASQ61 or BRAFWT/NRASWT melanoma metastases. The BRAFV600E PDX melanomas were acquired both prior to treatment with the BRAF inhibitor vemurafenib and after resistance had occurred, including six matched pairs. We find that PDX resemble their human donors’ melanomas regarding biomarkers, chromosomal aberrations, RNA expression profiles, mutational spectrum and targeted drug resistance patterns. Mutations, previously identified to cause resistance to BRAF inhibitors, are captured in PDX derived from resistant melanomThis melanoma PDX platform represents a comprehensive public resource to study both fundamental and translational aspects of melanoma progression and treatment in a physiologically relevant setting. Overall design: RNA sequencing of 4 melanoma PDX samples to validate the effects of a structural variant on BRAF mRNA in BRAF inhibitor resistant melanoma.
Publication Title
BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Samples were taken from surgically resected tumor specimens/metastases from patients with colorectal cancer. The expression profiles were determined using the Affymetrix GeneChip Human Exon 1.0 ST Array version 2.
Publication Title
Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Primary diffuse large B cell lymphomas of different immune-privileged sites (IP-DLBCL) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune-privileged sites and deletion of the HLA region, which suggests that IP-DLBCL represents a separate entity. To further investigate the nature of IP-DLBCL, we investigated site-specific genomic aberrations in 16 testicular, 9 central nervous system (CNS) and 15 nodal DLBCL using array-CGH. We also determined minimal common regions of gain and loss. Using robust algorithms, the array-CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations.
Publication Title
Genomic alterations and gene expression in primary diffuse large B-cell lymphomas of immune-privileged sites: the importance of apoptosis and immunomodulatory pathways.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
MYC translocations are the biologic hallmark of Burkitt lymphomas but also occur in other mature B-cell lymphomas. If accompanied by chromosomal breaks targeting the BCL2 and/or BCL6 oncogenes, these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas (DHLs); otherwise, the term single-hit lymphoma (SHL) is applied. In order to characterize the biologic features of these MYC+ lymphomas other than Burkitt lymphomas, we explored, after exclusion of molecular Burkitt lymphoma (mBL) as defined by gene expression profiling (GEP), the molecular, pathological and clinical aspects of 80 MYC translocation (MYC+) lymphomas (31 SHL, 26 BCL2+/MYC+, 14 BCL6+/MYC+, 6 BCL2+/BCL6+/MYC+ and 3 MYC+ lymphomas with unknown BCL6 status). Comparison of SHL and DHL revealed no difference in frequency of MYC partner (IG/non-IG), genomic complexity or MYC expression and no differences in GEP. DHL showed a more frequent GCB-like GEP and higher IGH and MYC mutation rates. GEP revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ DHL. BCL2+/MYC+ DHL showed a more frequent GCB-like GEP. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In contrast to mBL and lymphomas without MYC break, SHL and DHL patients had similar poor outcome. Our data suggest that after excluding mBL, MYC+ lymphomas could be biologically widely lumped without further need for subclassification.
Publication Title
Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Preterm infants are susceptible to neonatal inflammatory/infective diseases requiring drug therapy. The present study hypothesized that mRNA expression in the blood may be modulated by signaling pathways during treatment. The current study aimed to explore changes in global gene expression in the blood from preterm infants with the objective of identifying patterns or pathways of potential relevance to drug therapy. The infants involved were selected based on maternal criteria indicating increased risk for therapeutic intervention. Global mRNA expression was measured in 107 longitudinal whole blood samples using Affymetrix Human Genome U133 Plus 2.0 arrays; samples were obtained from 20 preterm infants. Unsupervised clustering revealed a distinct homogeneous gene expression pattern in 13 samples derived from seven infants undergoing continuous oxygen therapy. At these sampling times, all but one of the seven infants exhibited severe drops in peripheral capillary saturation levels below 60%. The infants were reoxygenated with 100% inspired oxygen concentration. The other samples (n=94) represented the infants from the cohort at time points when they did not undergo continuous oxygen therapy. Comparing these two sets of samples identified a distinct gene expression pattern of 5,986 significantly differentially expressed genes, of which 5,167 genes exhibited reduced expression levels during transient hypoxia. This expression pattern was reversed when the infants became stable, i.e., when they were not continuously oxygenated and had no events of hypoxia. To identify signaling pathways involved in gene regulation, the Database for Annotation, Visualization and Integrated Discovery online tool was used. Mitogen activated protein kinases, which are normally induced by oxidative stress, exhibited reduced gene expression during hypoxia. In addition, nuclear factor erythroid 2 related factor 2 antioxidant response element target genes involved in oxidative stress protection were also expressed at lower levels, suggesting reduced transcription of this pathway. The findings of the present study suggest that oxidative stress dependent signaling is reduced during hypoxia. Understanding the molecular response in preterm infants during continuous oxygenation may aid in refining therapeutic strategies for oxygen therapy.
Publication Title
Gene expression profiles in preterm infants on continuous long‑term oxygen therapy suggest reduced oxidative stress‑dependent signaling during hypoxia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of hexavalent chromium followed by anchorage-independent growth. The gene expression profiles were analyzed in the established cell lines.
Publication Title
Comparison of gene expression profiles in chromate transformed BEAS-2B cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Piwi proteins and Piwi-interacting small RNAs (piRNAs) have known functions in transposon silencing in the male germline of fetal and newborn mice. Both are also necessary for spermatogenesis in adult testes, however, their function here remains a mystery. Here, we use germ cell isolations and small RNA sequencing to show that most piRNAs in meiotic spermatocytes originate from clusters in intergenic non-repeat regions of DNA. The regulation of these piRNA clusters, including the processing of the precursor transcripts into individual piRNAs, is accomplished through mostly unknown processes. We present evidence for a regulatory mechanism for one such cluster, named cluster 1082B, located on chromosome 7 in the mouse genome, containing 788 unique piRNAs. The precursor transcript and individual piRNAs within the cluster are repressed by the Alkbh1 dioxygenase and the transcription repressor Tzfp, which are believed to be interaction partners in testis. We observe more than a thousand-fold upregulation of individual piRNAs in pachytene spermatocytes isolated from Alkbh1-/- and TzfpGTi/GTi testes. Repression is further supported by the identification of a 10 bp Tzfp recognition sequence contained within the precursor transcript. Downregulation of long interspersed elements 1 (LINE1) and intracisternal A-particle (IAP) transcripts in the Alkbh1-/- and TzfpGTi/GTi testes leads us to propose a potential role for the 1082B-encoded piRNAs in transposon silencing. Overall design: Characterization of small RNAs in mouse pachytene spermatocytes for wild-type (WT) and Alkbh1-/- and TzfpGTi/GTi, and mRNA in mouse pachytene spermatocytes for wild-type (WT) and Alkbh1-/-
Publication Title
Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung, and bladder cancers, and cardiovascular disease. The mechanisms behind arsenic's effects remain unclear, but recent research indicates that aresnic acts along sex-specific lines and may be an endocrine disruptor. The objective of this study was to evaluate the nature of gene expression chagnes among males and females exposed to arsenic contaminated water in Bangladesh at high and low dose exposures.The median wAs concentration for the low exposure group was 103 g/L for males and 117 g/L for females (range 50200 g/L). For the high exposure group, the median wAs concentration was 355 g /L for males (range 250-500 g /L) and 434 g/L for females (range 2321000 g /L). The PBMCs of males with high exposure compared to those with low exposure there were 534 differentially expressed genes (p <0.05); and for females with high exposure relative to low exposure there were 645 differentially expressed genes (p <0.05) in PBMCs of females.
Publication Title
Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sequentially acting Sox transcription factors in neural lineage development.
Sample Metadata Fields
Specimen part
View Samples