Immuno-chemotherapy regimens elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumors in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that drives aggressive tumor growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma.
Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers.
Specimen part, Cell line
View SamplesChromosome 1 pericentric heterochromatin rearrangements : potent drivers of nuclear architecture perturbations and gene deregulation in human B cell lymphoma
No associated publication
Cell line
View SamplesFemale sex steroid hormones, estradiol-17 (E2) and progesterone (P4) regulate reproductive function and gene expression in a broad range of tissues. Given the central role of the liver in regulating homeostasis including steroid hormone metabolism, we sought to understand how E2-17 and P4 interact to affect global gene expression in liver. Eight ovariectomized cows were randomly assigned to 4 treatment groups applied in a replicated Latin Square design: 1) No hormone supplementation, 2) E2-17 treatment (ear implant), 3) P4 treatment (intravaginal inserts), and 4) E2-17 combined with P4. After 14 d of treatment, liver biopsies were collected, allowing 28 d intervals between periods. Changes in gene expression in the liver biopsies were monitored using Affymetrix bovine-specific arrays. Treatment with E2-17 altered expression of 479 genes, P4 472 genes, and combined treatment significantly altered expression of 468 genes. In total, 578 genes exhibited altered expression including a remarkable number (346 genes) that responded similarly to E2-17, P4, or combined treatment. Additional evidence for similar gene expression effects of E2-17 and/or P4 were: principal component analysis placed almost every treatment array at a substantial distance from control arrays; Venn diagrams indicated overall treatment effects for most regulated genes; clustering analysis indicated the two major clusters had all treatments upregulating (cluster 1; 172 genes) or downregulating (cluster 2: 173 genes) expression. Thus, unexpectedly, common biological pathways are regulated by E2-17 and/or P4 in liver. Future studies are needed to elucidate mechanism(s) responsible for overlapping actions of E2-17 and P4 on the liver transcriptome. KEYWORDS: estradiol, progesterone, global gene expression, liver, cows.
No associated publication
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
Cell line
View SamplesFor this study, we selected, from the French Sarcoma Group (FSG) database, soft tissue sarcomas with no recurrent chromosomal translocations and for which a frozen tissue of the untreated primary tumor was available. Three hundred and ten sarcomas have been studied. They are split in two cohorts.
Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity.
Specimen part, Disease, Time
View SamplesIdentification of predictive markers of response to treatment is a major objective in breast cancer. A major problem in clinical sampling is the variability of RNA templates, requiring accurate management of tumour material and subsequent analyses for future translation in clinical practice. Our aim was to establish the feasibility and reliability of high throughput RNA analysis in a prospective trial.
Importance of pre-analytical steps for transcriptome and RT-qPCR analyses in the context of the phase II randomised multicentre trial REMAGUS02 of neoadjuvant chemotherapy in breast cancer patients.
Specimen part, Disease stage
View SamplesFor this study, we selected, from the French Sarcoma Group (FSG) database, soft tissue sarcomas with no recurrent chromosomal translocations and for which frozen tissue of the untreated primary tumor was available. One hundred and eighty-three cases were studied.
No associated publication
Specimen part, Disease
View SamplesTranscriptome analysis of 130 breast cancer samples (41 TNBC; 30 Her2; 30 Luminal B and 29 Luminal A), 11 normal breast tissue samples and 14 TNBC cell lines.
Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
Cell line
View SamplesTranscriptome analysis of 130 breast cancer samples (41 TNBC; 30 Her2; 30 Luminal B and 29 Luminal A), 11 normal breast tissue samples and 14 TNBC cell lines.
Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
Cell line
View SamplesThe distinction between primary and secondary ovarian tumors may be challenging for pathologists.
A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer.
Specimen part, Disease stage
View Samples