3659 results for "RNA AND sequencing OR transcriptome"

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• A Human Lymphoma Organoid Model for Evaluating and Targeting the Follicular Lymphoma Tumor Immune Microenvironment

  Heterogeneity in the tumor microenvironment (TME) of follicular lymphoma (FL) can affect clinical outcomes. We developed a new organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the native FL TME. We generated organoids from 12 FL patients at diagnosis, clinical progression, or relapse. These organoids were profiled with targeted DNA sequencing and mRNA sequencing. We evaluated the stability of organoids in culture at serial weekly timepoints (D0, D7, D14, D21). We treated organoids with CD19:CD3 or CD20:CD3 bispecific antibodies or unconjugated anti-CD20, anti-CD19, and anti-CD3 as a control, and profiled DNA/RNA at D11 to evaluate treatment response. This system is intended as a platform for advancing precision medicine efforts in FL through patient-specific modeling, high-throughput screening, TME signature identification, and treatment response evaluation.

  Study phs003410

• Genomic Characterization CS-MATCH-0007 Arm U

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm U is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with NF2 loss are treated with Defactinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002179

• Genomic Characterization CS-MATCH-0007 Arm C1

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm C1 is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with MET amplification are treated with Crizotinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002177

• Genomic Characterization CS-MATCH-0007 Arm P

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm P is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with PTEN loss by IHC are treated with the drug GSK2636771. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002152

• Genomic Characterization CS-MATCH-0007 Arm Z1B

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1B is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with CCND1, CCND2, and/or CCND3 amplifications are treated with Palbociclib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002180

• Genomic Characterization CS-MATCH-0007 Arm Q

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Q is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with HER2 amplification are treated with Kadcyla® (ado-trastuzumab emtansine). This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including tumor tissue and whole blood.

  Study phs001926

• The impact of mutational clonality in predicting the response to anti-PD-L1/PD-L1 in advanced urothelial cancer

  The advent of immune checkpoint inhibitors (ICI) has radically changed the management and therapeutic treatment landscape for patients with cancer. It has been shown that the use of these inhibitors can result in long-term complete remissions even in cases with advanced stages of the disease. However, only a small fraction of patients respond to the treatment. A better understanding of which factors could drive this clinical benefit is fundamental to building more accurate predictive biomarkers and developing alternative therapeutic options for patients who are unlikely to benefit. In order to address this issue, we have generated and analyzed whole exome sequencing (WES) and RNA sequencing (RNASeq) data from a cohort of metastatic urothelial carcinoma patients (N = 27) treated with ICI such as anti-PD-(L)1 monoclonal antibodies.

  Study EGAS00001007086

• Pilot study for Illumina TST170 NGS panel on cutaneous T cell lymphoma samples

  A number of genomic studies using next generation sequencing (NGS) techniques have attempted to understand the underlying genetic basis of cutaneous T-cell lymphoma and found alterations in genes that are involved in T-cell activation, NF-kB and JAK-signal transducer and activator of transcription (STAT) pathways. 8 diagnostic skin biopsy samples (2xplaque, 6xtumour) on FFPE blocks were selected from 8 MF patients (stage IB:n=1, IIB:n=6, IVA2:n=1). An H&E was performed in order to assess percentage of tumor cells, viable cells, necrosis and immune infiltration, to determine the number of slides required for NGS. Freshly cut unstained slides were manually macrodissected prior to DNA and RNA extraction. Targeted deep sequencing was performed using panel of 170 genes associated with common solid tumours (Illumina TruSight Tumour 170 NGS panel). VCF files generated via the Illumina’s Basespace platform.

  Study EGAS00001002567

• SPECTA RP-1759-AYA Sarcoma cohort

  EORTC-SPECTA RP1759 study focuses on cancers in adolescent and young adult (AYA), age 12 to 29 years. This study explicitly recruited AYA patients and therefore collected empirical data to bridge the molecular gap between pediatric and adult oncology. The initial pilot study, activated in February 2019 across Europe, aimed to recruit 100 AYA patients (aged 12-29 years) with newly diagnosed or relapsed high-grade gliomas and high-grade bone and soft tissue sarcomas. The primary objective of the pilot is to determine feasibility and recruitment rates. Here we submit the data from patients with newly diagnosed, recurrent intermediate or high-grade sarcoma that were collected and analyzed during the study. More specifically, we submit raw FASTQ files obtained from whole exome sequencing (WES) of matching tumor and blood samples, tumor RNA sequencing and DNA methylation profiling.

  Study EGAS00001005840

• Single cell multi-omic study of H3-K27M mutant diffuse midline glioma across age and location

  Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, but are also increasingly recognized in adult DMGs. Their potential heterogeneity at different ages and midline locations are vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We conducted multi-omic profiling of 50 H3-K27M mutant patient tumors. We performed deep full-length Smart-seq2 fresh single-cell (n=18) or frozen single-nucleus (n=25) RNA-sequencing (sc/snRNA-seq) of 43 tumors). We additionally analyzed the open chromatin profiles of 8 tumors utilizing the single-cell/nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq)

  Study EGAS00001006994

• Genomic Characterization of Pediatric Low-Grade Gliomas

  Pediatric low-grade gliomas (PLGGs) are the most common pediatric brain-tumor, with more than ten histologic subtypes recognized by the World Health Organization. We performed a genomic analysis of 230 PLGGs of which 73 had whole genome/RNA sequencing performed and show that MYB-QKI fusions define the seizure associated tumor, Angiocentric Glioma (AG). MYB-QKI fusions present in AGs contribute to tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression, and hemizygous loss of QKI, a tumor suppressor gene. Such interplay between three oncogenic mechanisms has diagnostic and therapeutic implications in AGs, and illustrates the functional complexity associated with rearrangements in cancer.

  Study phs001054

• Genomic landscape of Neutrophilic Leukemias of Ambiguous Diagnosis

  Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and unclassified myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN-U) are a group of rare, heterogeneous myeloid disorders. There is strong morphologic resemblance amongst these distinct diagnostic entities as well as lack of specific molecular markers and limited understanding of disease pathogenesis, which has made their diagnosis challenging. Treatment has remained empirical, resulting in dismal outcomes. We, therefore, performed whole exome and RNA-sequencing on a cohort of over 100 cases of these rare hematologic malignancies and present the most complete survey of the genomic landscape of these diseases to date. [Abstract from manuscript currently under review so copyright not yet determined]

  Study phs001799

• Single Cell Analysis of Psoriasis Resolution following IL-23 Blockade

  Full-thickness skin biopsies were obtained from five individuals with severe psoriasis who were receiving risankizumab treatment. Skin biopsies were taken from lesional and non-lesional sites at baseline, and from lesional sites at day 3 and day 14 of therapy. All biopsies were taken from site-matched areas on the lower back/buttocks. Single-cell RNA sequencing was performed using a 10x Genomics platform. Myeloid and fibroblast populations showed the strongest change in gene expression after 3 days. An inflammatory, transient WNT5A+/IL24+ fibroblast state was identified, which was elevated in abundance in lesional skin versus non lesional skin, and decreased after 14 days of treatment. R1 and R2 FASTQs files are available.

  Study phs003351

• Transcriptomic Profiling of Peripheral Immune Cells in a Trial of Ruxolitinib with Nivolumab for Anti-PD1 Non-Responsive cHL

  Treatment with checkpoint inhibitors is effective in multiple cancer types. However, even in cancers with high response rates such as Hodgkin lymphoma, some patients fail to respond or relapse following an initial response to checkpoint inhibitors. In this study, we examined patients enrolled in a clinical trial of ruxolitinib with nivolumab in relapsed or refractory Hodgkin lymphoma (NCT03681561). Patients relapsed or refractory to anti-PD1 therapy received ruxolitinib for 8 days followed by nivolumab every 4 weeks and continued ruxolitinib twice daily. For this transcriptomic study, peripheral blood mononuclear cells (PBMCs) were collected at baseline and 8 days of ruxolitinib therapy and analyzed by single-cell and bulk RNA-sequencing.

  Study phs003601

• Single cell RNAseq 7 days - Calprotectin in vitro effects on human early hematopoiesis

  To explore the effects of calprotectin (CAL) on early hematopoiesis, we incubated CD34+ cells from four healthy donors for 7 days in the presence of stem cell factor (SCF), FLT3-ligand and thrombopoietin (TPO) without and with CAL, interleukin-6 (IL6) and the IL6_CAL combination before collecting cells. We performed the same experiment with CD34+ cells collected from three patients with JAK2-V617F-mediated myelofibrosis (MF). A total of 135,545 cells from healthy donors and 111,725 cells from myelofibrosis patients were analyzed by single-cell RNA sequencing (scRNA-seq) using the 10X Chromium droplet-based platform. Single cell RNAseq 7 days - Normal and tumor samples 4 conditons : -Control - Calprotectin - IL-6 - Calprotectin+IL-6

  Study EGAS50000000455

• Bulk ATACseq 7days - Calprotectin in vitro effects on human early hematopoiesis

  To explore the effects of calprotectin (CAL) on early hematopoiesis, we incubated CD34+ cells from four healthy donors for 7 days in the presence of stem cell factor (SCF), FLT3-ligand and thrombopoietin (TPO) without and with CAL, interleukin-6 (IL6) and the IL6_CAL combination before collecting cells. We performed the same experiment with CD34+ cells collected from three patients with JAK2-V617F-mediated myelofibrosis (MF). A total of 135,545 cells from healthy donors and 111,725 cells from myelofibrosis patients were analyzed by single-cell RNA sequencing (scRNA-seq) using the 10X Chromium droplet-based platform. Bulk ATACseq 7days - Normal and tumor samples 4 conditons : -Control - Calprotectin - IL-6 - Calprotectin+IL-6

  Study EGAS50000000456

• Pathologically Expanded Peripheral B Cell-Helper T Cells in Rheumatoid Arthritis

  PROSET-HD aims to identify and study immune cell populations altered in patients with autoimmune and inflammatory diseases. We have identified a population of PD-1hi CXCR5- 'peripheral helper' T (Tph) cells that are expanded in the joints and circulation of patients with seropositive rheumatoid arthritis. This T cell population uniquely combines potent B cell-helper function with a migratory program that directs homing to inflamed tissues. RNA sequencing was performed on sorted memory CD4+ T cell subpopulations to compare the global gene expression profiles of PD-1hi CXCR5- CD4+ T cells, PD-1hi CXCR5+ follicular helper T cells, and other T cell populations obtained from blood of rheumatoid arthritis patients.

  Study phs001262

• Transcriptomic profiling of proximal and distal regions of human long head biceps tendon

  Tendinopathy is a prevalent musculoskeletal disorder marked by extracellular matrix disorganization, collagen remodeling, vascular ingrowth, and pain, yet its underlying molecular mechanisms remain insufficiently defined. The long head of the biceps tendon (LHBT) is particularly prone to mechanical overload and early degenerative changes, making it a relevant model for studying tendon pathology. In this study, we aimed to characterize region-specific gene expression changes along the LHBT to better understand the molecular basis of degeneration. We collected paired proximal and distal LHBT tissue from patients undergoing rotator cuff repair surgery and performed bulk RNA sequencing. This approach enables the identification of degeneration-associated transcriptional signatures while minimizing inter-patient variability.

  Study EGAS50000001454

• Origins and timing of emerging lesions in advanced renal cell carcinoma

  Renal cell carcinoma (RCC) with venous tumor thrombus (VTT) arising from the primary tumor occurs in ~10% of cases and is thought to represent more advanced disease. RCC with VTT and distant metastasis provides unique opportunities to examine the origins and relative timing of tumor lesion emergence and to identify molecular correlates with disease state. We performed multi-region exome and RNA sequencing analysis of a clinical cohort of 16 RCC patients with VTT, with eight patients also having sequenced metastasis, to examine which genomic alterations, biological pathways, and evolutionary processes contribute to VTT and metastasis, and to ask whether metastasis typically arises directly from VTT or is independent of VTT.

  Study EGAS00001005897

• Tumor microenvironment study of ovarian granulosa cell tumors

  Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few 41 effective treatments for recurrent disease. The objective of this study was to compare global gene expression profiles and characterize the tumor microenvironment (TME) of primary and recurrent aGCTs in order to identify correlates of disease recurrence. Total RNA sequencing was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. A total of 31 differentially expressed genes were identified between primary and recurrent aGCT. TME analysis demonstrated significantly higher fractions of neutrophils and macrophages in recurrent tumors in conjunction with significantly lower fractions of cancer-associated fibroblasts and endothelial cells.

  Study EGAS00001006478

• Carboxylesterase 1 mediates a distinctive metabolic profile of dendritic cells to attain an inflammatory phenotype

  The metabolic profile of dendritic cells (DCs) shapes their phenotype and functions. Carboxylestrase 1 (CES1) enzyme is highly expressed in mononuclear myeloid cells however its exact role in DCs is elusive. We used a CES1 inhibitor (WWL113) and genetic overexpression to explore the role of CES1 in DCs differentiation in inflammatory models. CES1 expression was analyzed during CD14+ monocytes differentiation to DCs (MoDCs) using quantitative PCR. CES1 Inhibitor (WWL113) was applied during MoDCs differentiation. Surface markers, secreted cytokines, lactic acid production, phagocytic and T cell polarization capacity were analyzed. Transcriptomic and metabolic profile were assessed with RNA-sequencing and mass spectrometry. Cellular respiration was assessed with seahorse respirometry. Transgenic mice were used to assess CES1 overexpression in DCs in inflammatory models. CES1 expression peaks early during MoDCs differentiation. Pharmacological inhibition of CES1 led to higher expression of CD209, CD86 and MHCII. WWL113 treated MoDCs secreted higher quantities of IL6, IL8, TNF and IL10 and demonstrated stronger phagocytic ability and higher capacity to polarize Th17 differentiation in autologous DCs-T cells co-culture model. Transcriptomic profiling revealed enrichment of multiple inflammatory and metabolic pathways. Functional metabolic analysis shows impaired maximal mitochondrial respiration capacity, increased lactate production and decreased intracellular amino acids and TCA intermediates. Transgenic human CES1 overexpression in murine DCs generated less inflammatory phenotype and increased resistance to T cell mediated colitis. In conclusion, CES1 inhibition directs DCs differentiation towards more inflammatory phenotype, that shows stronger phagocytic capacity and supports Th17 skewing. This is associated with disrupted mitochondrial respiration and amino acids depletion.

  Study EGAS50000000230

• Longitudinal_profiling_of_the_immune_response_to_Plasmodium_vivax_in_naive_hosts_by_RNA_sequencing

  Plasmodium vivax offers unique challenges for control and elimination, and may prove a tougher hurdle to overcome than Plasmodium falciparum. And yet compared to P. falciparum we know very little about the innate and adaptive immune responses that need to be harnessed to reduce disease and transmission. We recently generated a blood bank of a new clonal field isolate of P. vivax (PvW1) for human challenge studies and used systems immunology tools to track the host response throughout infection and convalescence. As part of this study, RNA-sequencing was used to resolve changes in whole blood gene expression through time in 6 volunteers (7-9 time-points per volunteer). In summary, these data show that P. vivax induces two distinct transcriptional programmes in whole blood during and after infection. During infection, transcriptional profiling reveals the rapid mobilisation of an emergency myeloid response, which leads to systemic inflammation and the recruitment of all major T cell subsets into lymphoid tissues. Six days after infection, this innate response subsides and a transcriptional signature of proliferation is revealed. This most likely represents widespread activation of lymphocytes, which return to the circulation after parasite clearance - transcriptional profiling of T cells at this time-point could therefore reveal the outcomes of critical cell-cell interactions that take place within the spleen during infection. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001003847

• MATISSE WES and bulk RNA-sequencing data

  High-risk cutaneous squamous cell carcinoma is frequently seen in frail, elderly patients and often requires mutilating surgical treatment and adjuvant radiotherapy (RT). The MATISSE trial (NCT04620200) was conducted to improve clinical prospects in CSCC patients eligible for extensive curative surgery, and evaluated early treatment response and immune dynamics following ultra-short neoadjuvant immunotherapy prior to standard of care surgery with or without radiotherapy. Fifty patients were randomized to receive two courses of nivolumab 3 mg/kg (NIVO, weeks 0&2) or nivolumab 3 mg/kg (weeks 0&2) and one course of ipilimumab 1 mg/kg (week 0 only, NIVO/IPI before surgery at week 4, with the primary objective being histopathological response based on residual viable tumor cells in the surgical specimen. Ten patients choose not to undergo surgery, of whom nine reached a clinical complete response during follow up, and were disease-free at median 34 months follow up. Serial tumor and blood samples at baseline, week 1, week 2 and week 4, enabled to investigate dynamical changes through bulk WES and RNA sequencing to potentially aid future de-escalation trials.

  Study EGAS50000001003

• Single cell RNA sequencing of synovial B cells in early Rheumatoid Arthritis

  Rheumatoid Arthritis (RA) is a prevalent autoimmune disease characterized by inflammation of the peripheral joints and occurence of autoantibodies, i.e. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA), in circulation. Previous studies have shown that there are memory B cells and autoantibody producing plasma cells present in the joint tissue of patients with long-standing RA. However, it has remained unclear, whether these B cell populations are already present in the joint tissue of patients at the disease onset and whether these are autoreactive. Here, we used a single cell RNA sequencing approach to dissect the B cell repertoire at this early timepoint. We found evidence for B and T cell interaction and presence of memory and plasma cell pools in ACPA- and ACPA+ RA. Our results demonstrated clonal relationships between the memory and plasma cell compartments and autoreactivity within the plasma cell pool. These findings challenge our understanding of the local adaptive immune response in the joints of ACPA- and ACPA+ RA patients with direct implications for B and T cell targeting therapy in both patient subgroups.

  Study EGAS00001005144

• Characterization of Immune Evasion in Merkel Cell Carcinoma

  Merkel cell carcinoma (MCC) is a rare, neuroendocrine skin carcinoma that is caused by the Merkel cell polyomavirus (MCPyV) in 80% of cases and by ultraviolet (UV) damage in 20% of cases. MCC should theoretically elicit a strong cytotoxic T cell response due to the high neoantigen and viral antigen burden in MCPyV- and MCPyV+ MCC, respectively. However, MCC often escapes immune recognition and is associated with very poor prognosis at advanced stages. To systemically identify mechanisms of immune evasion in MCC, we established 11 robust MCC lines from either primary tumors or patient-derived xenografts (7 MCPyV+ and 4 MCPyV-). We then characterized these tumors and cell lines by whole exome sequencing (WES), RNA-sequencing, scRNA-sequencing, ATAC-seq, and whole genome bisulfite sequencing (WGBS). We also studied MCC transcriptional subtypes, utilizing bulk and scRNA-sequencing datasets of patient-derived tumors and cell lines to investigate profiles of neuroendocrine gene expression. The genes linked below define either a neuroendocrine or a non-neuroendocrine phenotype presence within MCC tumors.

  Study phs002260