11935 results for "cancer rna-seq"

in 13.99 milliseconds.

• T-VEC CBCL scRNA

  We are presenting raw and processed data of our study where we analyze fine-needle aspirate (FNA) samples of primary cutaneous B-cell lymphoma patients undergoing oncolytic virotherapy (https://clinicaltrials.gov/ct2/show/NCT03458117). We are uploading single cell RNA-sequencing and immune repertoire profiling data of 29 FNA samples from four pCBCL patients. The four patients have three different subtypes of primary cutaneous B-cell lymphoma: pCDLBCL-LT, pCFCL and pCMZL. The samples are taken at different time points following T-VEC injection (from baseline up to 91 days after injection). We are uploading the sequences in BAM format and the outputs of the cellranger pipeline (count matrices and filtered VDJ contigs) in CSV format.

  Dataset EGAD00001006829

• Massive parallel RNA sequencing of highly purified mesenchymal cells derived from bone marrow specimens of 3 Diamond-Blackfan anemia cases

  Highly purified mesenchymal cells (CD45-/7AAD-/CD235a-/CD31-/CD271+/CD105+) were prospectively FACS-isolated from bone marrow specimens of 3 Diamond-Blackfan anemia (DBA) cases. This data set, comprising 3 DBA cases, is used as complement to 45 low-risk myelodysplastic syndrome (LRMDS) and 4 Shwachman-Diamond syndrome (SDS) cases to demonstrate aberrant inflammatory signaling as a common mechanism in pre-leukemia syndromes to induce genotoxic stress in hematopoietic stem cells. In addition, this data set is used to determine different overlapping gene expression signatures in pre-leukemia syndromes compared to gene expression profiles of highly purified mesenchymal cells of healthy donors.

  Dataset EGAD00001002661

• MPM cell lines

  RNA-sequencing data for 12 MPM cell lines treated with 0.1% DMSO or 1 µM palbociclib for 9-10 days. Experiment was performed in duplicates for sensitive cells (MPM08, MPM21, MPM38, MPM57, MPM59, Meso11, Meso13, Meso34 and Meso56) and only once for resistant cells (MPM31, MPM34 and MPM36) except for Meso11 which was done in triplicates. For Meso11, Meso13, Meso34 and Meso56, a drug washout of 48 hours was also performed. 4 MPM cell lines (MPM31, MPM34, MPM59 and MPM66) were also analyzed in untreated condition. 2 FASTQ files for each sample (n=56) (paired)

  Dataset EGAD00001008741

• Massive parallel RNA sequencing of highly purified mesenchymal cells derived from bone marrow specimens of 4 Shwachman-Diamond syndrome cases

  Highly purified mesenchymal cells (CD45-/7AAD-/CD235a-/CD31-/CD271+/CD105+) were prospectively FACS-isolated from bone marrow specimens of 4 Shwachman-Diamond syndrome (SDS) cases. This data set, comprising 4 SDS cases, is used as complement to 45 low-risk myelodysplastic syndrome (LRMDS) and 3 Diamond-Blackfan anemia (DBA) cases to demonstrate aberrant inflammatory signaling as a common mechanism in pre-leukemia syndromes to induce genotoxic stress in hematopoietic stem cells. In addition this data set is used to determine different overlapping gene expression signatures in pre-leukemia syndromes compared to gene expression profiles of highly purified mesenchymal cells of healthy donors.

  Dataset EGAD00001002660

• Target-capture sequencing of FFPE tumor samples from patients diagnosed with NKTL

  211 NKTL FFPE specimens were screened for somatic mutations using deep targeted capture sequencing. FFPE rolls or slides were extracted using QIAamp DNA FFPE Tissue kit (QIAGEN). The FFPE genomic DNA was treated with NEBNext FFPE DNA Repair Mix and assessed by Quant-it PicoGreen dsDNA Assay Kit (Invitrogen). The library was generated from 10-200 ng DNA with SureSelectXT Low Input Target Enrichment System for Illumina Paired-End Sequencing Library (Agilent Technologies) according to manufacturer’s instructions. RNA based probe was designed with SureDesign (Agilent Technologies) to target-capture 140 genes. Next, the captured libraries were pooled in equimolar concentration and sequenced on Illumina Novaseq 6000 platform with SP or S1 chip.

  Dataset EGAD00001005303

• Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens

  In this study we performed whole genome sequencing on matched tumor-normal CD138+ bone marrow mononuclear cells from 60 patients with newly diagnosed multiple myeloma treated with daratumumab, carfilzomib, lenalidomide, and dexamethasone (NCT03290950-MANHATTAN trial). In addition, we performed 5’-single-cell RNA-sequencing (10X Genomics) coupled with V(D)J sequencing and capture of the surface protein markers (TotalSeq-C, Biolegend) of the CD138- bone marrow mononuclear cells to interrogate the composition of the immune microenvironment at baseline and after eight cycles of induction therapy in 22 patients with newly diagnosed multiple myeloma. Samples were multiplexed using hashtag oligo.

  Dataset EGAD00001011132

• Liquid Biopsy Versus Tissue Biopsy to Assess Acquired Resistance and Tumor Heterogeneity in Gastrointestinal Cancers

  Tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique molecular resistance alterations in different metastatic lesions in an individual patient, under the selective pressure of therapy1-3. Studies have suggested that liquid biopsy may better capture the heterogeneity of acquired resistance, but systematic, direct comparisons of post-progression liquid vs. standard single-lesion tumor biopsies are lacking. In a prospective cohort of 44 patients with molecularly-defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of post-progression liquid vs. tumor biopsy revealed that liquid biopsy more frequently identified clinically-relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not detected in matched tumor biopsy in 78% of cases. Whole-exome sequencing of serial cell-free DNA, tumor biopsies and rapid autopsy specimens elucidated geographic and evolutionary characteristics of heterogeneity. Our data suggest that acquired resistance is frequently characterized by profound tumor heterogeneity and highlight the potential clinical utility of liquid biopsy. Burrell, R. A. & Swanton, C. Tumour heterogeneity and the evolution of polyclonal drug resistance. Molecular oncology 8, 1095-1111, doi:10.1016/j.molonc.2014.06.005 (2014). Misale, S. et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 486, 532-536, doi:10.1038/nature11156 (2012). Ahronian, L. G. et al. Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations. Cancer Disco 5, 358-367, doi:10.1158/2159-8290.Cd-14-1518 (2015).

  Study phs001853

• Durable clinical impacts and mechanisms of action and resistance in histone K27 methylation-targeting epigenetic therapy

  Epigenomes allow the rectification of disordered cancer gene expressions, thereby providing new targets for pharmacological interventions in cancer therapy. The clinical utility of targeting histone H3 lysine tri-methylation (H3K27me3) as an epigenetic hallmark has been demonstrated. However, in actual therapeutic settings, the mechanism by which H3K27me3-targeting therapies exert their effects and the response of tumor cells remain unclear. Here we show the potency and mechanisms of action and resistance of a newly developed EZH1/2 dual inhibitor, valemetostat, in the clinical trials of patients with adult T-cell leukemia/lymphoma (ATL). Valemetostat administration reduced the tumor size and demonstrated durable clinical benefits. Integrative single-cell analyses of patients before and after the administration of valemetostat showed that valemetostat abolishes the highly condensed chromatin structure formed by the plastic H3K27me3 and neutralizes multiple gene loci, such as tumor suppressor genes. Nevertheless, subsequent long-term treatment encounters the emergence of resistant clones with reconstructed aggregate chromatin that closely resemble the pre-dose state. The acquired mutations at the EZH2???compound interface result in the propagation of the clones with re-increased H3K27me3. In patients free of this mutation, TET2 mutation or elevated DNMT3A expression causes similar chromatin recondensation through de novo DNA methylation at the H3K27me3-associated regions. We identified subpopulations with distinct metabolic and gene translation characteristics implicated in primary susceptibility until the acquisition of the heritable (epi)mutations. Targeting chromatin homeostasis might provide opportunities for further sustained epigenetic cancer therapies.

  Study JGAS000553

• Sequence analysis of colorectal serrated lesions

  Recent studies have shown that colorectal serrated lesions, which include sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), are precursors of colorectal cancer. However, the molecular mechanisms underlying the carcinogenesis, particularly in TSAs, remain largely uncharacterized. To clarify their molecular and clinicopathological characteristics, we performed mutation and methylation analyses of cancer-associated genes in 78 serrated lesions, including TSAs, SSAs and microvesicular hyperplastic polyps. Target exon sequence analysis was performed with 39 genes, including genes known to be frequently mutated in colorectal cancers and/or serrated lesions. We also used bisulfite pyrosequencing to assess the methylation status of various cancer-associated genes and marker genes of the CpG island methylator phenotype (CIMP). The prevalence of mutations in genes associated with Wnt signaling was significantly higher in TSAs than SSAs (65% vs. 28%, p < 0.01). Among those, RNF43 mutations were observed in 38% of TSAs and 17% of SSAs. In immunohistochemical studies of 39 serrated lesions, the prevalence of abnormal nuclear ?-catenin accumulation was significantly higher in TSAs (57%) than SSAs (8%) (P = 0.01). SMOC1 methylation was detected in 54% of TSAs but in no SSAs (p < 0.01). Additionally, SMOC1 methylation was more prevalent among TSAs with KRAS mutation (82%) than with BRAF mutation (38%, p = 0.03). Lesions with CIMP-high or RNF43 mutations were detected only in TSAs with BRAF mutation, suggesting two distinct carcinogenic pathways in TSAs. Mutations in genes associated with Wnt signaling play a greater role in the carcinogenesis of TSAs than SSAs.

  Study JGAS000217

• Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles

  Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs. We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed. We observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2, but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time. These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.

  Study EGAS00001004063