Filters
Technology
Platform
SRP019994
Homo sapiens
99 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for LMS. We demonstrate the existence of 3 molecular subtypes in a cohort of 99 cases and an independent cohort of 82 LMS. Two new FFPE tissue-compatible diagnostic immunohistochemical markers are identified: LMOD1 for subtype I LMS and ARL4C for subtype II LMS. Subtype I and subtype II LMS are associated with good and poor prognosis, respectively. The LMS subtypes show significant differences in expression levels for genes for which novel targeted therapies are being developed. Overall design: Gene expression profiling was performed by 3'' End RNA Sequencing (3SEQ), a next generation sequencing approach that does not rely on frozen tissue but can be performed on archival FFPE tissue. Samples included 99 LMS, 6 Undifferentiated Pleomorphic Sarcomas (UPS), 3 leiomyomas, 4 normal myometrium samples, and 1 case of Lymphangioleiomyomatosis (LAM). This study only includes the 99 LMS Samples. After gene expression levels were quantified by 3SEQ analysis pipeline, Consensus Clustering with bootstrap method was used to determine that the dataset contained three robust subtypes, and Silhouette analysis was performed to validate the subtype assignments. Two class SAM analysis (Significance Analysis of Microarrays) was performed to identify genes expressed differentially between each subtype of LMS with FDR of 0.05. Immunohistochemical staining was used to validate the potential diagnostic and prognostic markers from 3SEQ data on a tissue microarray.
Publication Title
Molecular subtyping of leiomyosarcoma with 3' end RNA sequencing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Enforced expression of the homeobox transcription factor HOXB4 has been shown to enhance hematopoietic stem cell (HSC) self-renewal and expansion ex vivo and in vivo. In order to investigate the largely unknown downstream targets of HOXB4 in hematopoietic progenitor cells, HOXB4 was constitutively overexpressed in the primitive hematopoietic progenitor cell line, EML. Gene expression differences were compared between KLS (c-Kit+, Lin-, Sca-1+)-EML cells that overexpressed HOXB4 (KLS-EML-HOXB4) to control KLS-EML cells that were transduced with vector alone. ChIP-chip was used to identify promoter regions bound by HOXB4.
Publication Title
Downstream targets of HOXB4 in a cell line model of primitive hematopoietic progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells.
Publication Title
BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
RNA polymerase III (Pol III) is an essential enzyme responsible for the synthesis of several small non-coding RNAs, a number of which are involved in mRNA translation. Recessive mutations in POLR3A, encoding the largest subunit of Pol III, cause POLR3-related hypomyelinating leukodystrophy (POLR3-HLD), characterized by deficient central nervous system myelination. Identification of the downstream effectors of pathogenic POLR3A mutations has been so far elusive. Here, we used CRISPR-Cas9 to introduce the POLR3A mutation c.2554A>G (p.M852V) into human cell lines and assessed its impact on Pol III biogenesis, nuclear import, DNA occupancy, transcription, and protein levels. Transcriptomic profiling uncovered a subset of transcripts vulnerable to Pol III hypofunction, including a global reduction in tRNA levels. The brain cytoplasmic BC200 RNA (BCYRN1), involved in translation regulation, was consistently affected in all our cellular models, including patient-derived fibroblasts. Genomic BC200 deletion in an oligodendroglial cell line led to major transcriptomic and proteomic changes, having a larger impact than those of POLR3A mutations. Upon differentiation, mRNA levels of the MBP gene, encoding myelin basic protein, were significantly decreased in POLR3A-mutant cells. Our findings provide the first evidence for impaired Pol III transcription in cellular models of POLR3-HLD and identify several candidate effectors, including BC200 RNA, having a potential role in oligodendrocyte biology and involvement in the disease. Overall design: Gene expression profiling of Pol III transcripts in control and POLR3A-mutated cell lines (HEK293 and MO3.13) using RNA-seq and small RNA-seq; ChIP-seq of FLAG-tagged POLR3A-WT and mutated POLR3A-M852V
Publication Title
Leukodystrophy-associated <i>POLR3A</i> mutations down-regulate the RNA polymerase III transcript and important regulatory RNA <i>BC200</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000, IlluminaGenomeAnalyzerIIx
Description
Leiomyosarcoma (LMS) is a malignant neoplasm of smooth muscle and is an aggressive soft tissue tumor, have complex genetic abnormalities and could be defined as three molecular subtypes. Since that the molecular heterogeneity of LMS, the pathogenesis analysis per subtype will be highly necessary and helpful to understand the etiology of this more common sarcoma. Overall design: Within this study, we collected four Myometrium, three Leiomyoma, three LMS cell lines and 99 LMSs (GSE45510), performed the system-wide gene expression profiling by 3''end RNA Sequencing, and found that there are significant different molecular pathways along the pathogenesis for those three molecular subtypes.
Publication Title
Clinically Relevant Molecular Subtypes in Leiomyosarcoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Background: Undifferentiated pleomorphic sarcoma (UPS), used to be called malignant fibrous histiocytoma (MFH), is a malignant soft tissue tumor of uncertain origin, and is characterized by morphology. UPS often share similar morphological characters with other sarcomas, especially Leiomyosarcoma. Leiomyosarcoma (LMS) is another malignant soft tissue sarcoma with complex genomic abnormalities, origin from smooth muscle. As a result, development of gene signature and/or biomarkers distinguishing UPS and LMS will definitely help the pathologist to precisely diagnose those patients. However, in the past, UPS was reported to be indistinguishable with LMS by genomic profiles. Methods and Results: In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. Overall, UPS was undistinguished with LMS by 3SEQ data, however, when we stratified LMS into three subtypes, UPS was shown to share similar expression pattern with Subtype II LMS, but had distinct molecular expression patterns with Subtype I and Subtype III LMS. Additional Immunohistochemistry staining by using LMS Subtype I and Subtype II markers validated that UPSs were positive for Subtype II marker ARL4C, but negative for Subtype I marker LMOD1. Furthermore, CD4 was shown to be significantly more highly expressed in UPS than LMS in both mRNA and protein levels. Conclusion: This study first reported that UPS shared similar gene expression pattern with subtype II LMS and UPS recapitulated the expression profiles of subtype II LMS. Overall design: In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. In order to explore the molecular differences between UPS and LMS, We analyzed the expression data by SAMseq to identify the genes which were significantly differently expressed between UPS and LMS, between UPS and each LMS subtype.
Publication Title
Clinically Relevant Molecular Subtypes in Leiomyosarcoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We report findings that illuminate a dynamic metastasis pathway in the common pediatric brain tumor medulloblastoma.
Publication Title
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Enriched tumor epithelium from 61 primary and metastasis tumor specimens was obtained by laser capture microdissection (LCM) as previously described (Boersma et al., 2007). In brief, frozen 8-m serial sections from OCT-preserved frozen tissues were prepared and mounted on plain, uncharged microscope slides. One Hematoxylin/eosin-stained section of each specimen was reviewed by a pathologist to confirm diagnosis and presence of tumor. The pathologist indicated which representative sections of the tumors should be microdissected. LCM was performed with the Pixcell II LCM system (Arcturus, Mountain View, CA). Total RNA was isolated using the PicoPure protocol (Arcturus, Mountain View, CA). The mRNA was amplified with two linear amplification steps by in vitro transcription using the MEGAscript T7 kit (Ambion, Austin, TX) followed by the labeling step using the BioArray HighYield RNA Transcript Labeling Kit T3 from Enzo Life Sciences (Farmingdale, NY). Labeled cRNA was hybridized onto Affymetix GeneChip HG-U133 Plus 2.0 Arrays.
Publication Title
Integrative genomic and transcriptomic characterization of matched primary and metastatic liver and colorectal carcinoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 488 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We used Affymetrix microarray profiling to analyze gene expression patterns in healthy donor liver as well as tumor and paired non-tumor tissue of HCC patients.
Publication Title
A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples