Gene expression changes were analyzed in 2 acute lymphoblastic leukemia cell lines treated with the GSK126 EZH2 inhibitor using Affymetrix Human Genome U133 Plus 2.0 arrays.
A687V EZH2 is a driver of histone H3 lysine 27 (H3K27) hypertrimethylation.
Cell line, Treatment, Time
View SamplesNoncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease and to reveal uncharacterized aspects of tumor biology. Here we discover 121 unannotated prostate cancer–associated ncRNA transcripts (PCATs) by ab initio assembly of high-throughput sequencing of polyA+ RNA (RNA-Seq) from a cohort of 102 prostate tissues and cells lines. We characterized one ncRNA, PCAT-1, as a prostate-specific regulator of cell proliferation and show that it is a target of the polycomb repressive complex 2 (PRC2). We further found that patterns of PCAT-1 and PRC2 expression stratified patient tissues into molecular subtypes distinguished by expression signatures of PCAT-1–repressed target genes. Taken together, our findings suggest that PCAT-1 is a transcriptional repressor implicated in a subset of prostate cancer patients. These findings establish the utility of RNA-Seq to identify disease-associated ncRNAs that may improve the stratification of cancer subtypes. Overall design: 21 prostate cell lines sequenced on the Illumina Genome Analyzer and GAII. Variable number of replicates per sample. RNA-Seq data from prostate cancer tissues used in this study will be made available on dbGAP.
Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression.
No sample metadata fields
View SamplesMucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma with distinctive morphologic and cytogenetic features. Here we carry out whole exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n=22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSGs) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes while other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to bi-allelic alterations in these TSGs. As a read-out of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. To identify transcriptional targets of the Hippo pathway in kidney we performed PTPN14 knockdown followed by RNA-seq in 2 kidney cancer cell lines (CAKI-1 and A-704) and a normal kidney epithelial cell line (HK-2). PTPN14 siRNAs were first functionally validated in a MCF-7 TEAD reporter luciferase stable cell line. Both siRNAs showed comparable knockdown efficiency and significantly increased luciferase reporter activity. In 2 of the kidney cell lines PTPN14 knockdown increased cell proliferation compared to non-target controls. While we observed excellent correlation between genes dysregulated by either PTPN14 or LATS1 knockdown within each cell line (HK2, CAKI-1 and A704), the overlap across the 3 cell lines was only 23 genes. Further, these 23 genes did not show concordant differential expression in MTSCC tumors. Overall, these results illustrate the marked tissue specificity of Hippo pathway targets.Finally, taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. Overall design: Cell lines (CAKI-1, HK2 or A704) were either transfected with 2 independent siRNAs or non-target controls. Forty eight hours post transcription total RNA was isolated and subjected to RNA-seq analysis
Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney.
Specimen part, Disease, Disease stage, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.
Specimen part, Cell line, Treatment
View SamplesWe studied transcriptional changes by Affymetrix human microarrays in DLBCL cell lines as a result of treatment with GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.
Specimen part, Cell line, Treatment
View SamplesWe studied transcriptional changes by Affymetrix human microarrays in 2 DLBCL cell lines as a result of shRNA mediated knockdown of EZH2.
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.
Specimen part, Cell line, Treatment
View SamplesAim was to identify cellular factors that regulate HPV-16 late gene expression at the level of RNA processing
Heterogeneous Nuclear Ribonucleoprotein C Proteins Interact with the Human Papillomavirus Type 16 (HPV16) Early 3'-Untranslated Region and Alleviate Suppression of HPV16 Late L1 mRNA Splicing.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC.
Specimen part, Cell line, Treatment
View SamplesEpigenetic dysregulation has emerged as an important mechanism in cancer. Alterations in epigenetic machinery have become a major focus for new targeted therapies. The current report describes the discovery and biological activity of a cyclopropylamine containing inhibitor of Lysine Demethylase 1 (LSD1), GSK2879552. This small molecule is a potent, selective, orally bioavailable, mechanism-based irreversible inhibitor of LSD1. A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) is sensitive to LSD1 inhibition. The subset of SCLC lines and primary samples that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes suggesting this may be used as a predictive biomarker of activity. The targeted mechanism coupled with a novel predictive biomarker make LSD1 inhibition an exciting potential therapy for SCLC, a highly prevalent, rarely cured, tumor type representing approximately 15% of all lung cancers.
A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC.
Cell line, Treatment
View SamplesCotton is one of the most commercially important Fiber crops in the world and used as a source for natural textile Fiber and cottonseed oil. The fuzzless-lintless ovules of cotton mutants are ideal source for identifying genes involved in Fiber development by comparing with Fiber bearing ovules of wild-type. To decipher molecular mechanisms involved in Fiber cell development, transcriptome analysis has been carried out by comparing G. hirsutum cv. MCU5 (wild-type) with its fuzzless-lintless mutant (MUT). Cotton bolls were collected at Fiber initiation (0 dpa/days post anthesis), elongation (5, 10 and 15 dpa) and secondary cell wall synthesis stage (20 dpa) and gene expression profiles were analyzed in wild-type and MUT using Affymetrix cotton GeneChip Genome array.
Functional genomics of fuzzless-lintless mutant of Gossypium hirsutum L. cv. MCU5 reveal key genes and pathways involved in cotton fibre initiation and elongation.
Specimen part
View Samples