12214 results for "cancer rna-seq"

in 42.53 milliseconds.

• Mechanism of action and resistance to Trastuzumab Deruxtecan in patients with metastatic breast cancer: the DAISY trial

  195 exome sequencing samples

  Dataset EGAD00001011110

• Genome and transcriptome sequence data from a neurofibromatosis type 1 (NF1) tumor patient

  Genome and transcriptome sequence data from a neurofibromatosis type 1 (NF1) patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015266

• Exploratory novel biomarker and resistance mechanism of milademetan, an MDM2 inhibitor, in MDM2 amplified intimal sarcoma from an open-label phase 1b/2 trial ���NCCH1806/MK004���

  Amplified Murine double minute 2 (MDM2) is found in > 70% of intimal sarcoma, known as one of the ultra-rare sarcomas. Milademetan (DS3032, RAIN-32) is a novel, specific, small-molecule MDM2 inhibitor that disrupts MDM2 and the tumor suppressor protein p53 interactions in tumor cells. We conducted a phase 1b/2 trial (Trial registration No: JMA-IIA00402) in patients with amplified MDM2 wild-type TP53 intimal sarcoma as a sub-study under the nationwide large registry for rare cancers in Japan (MASTERKEY Project). Eleven patients were enrolled, and ten were included in the efficacy analysis. Two (20%) patients had durable responses for > 15 months. Milademetan provided clinical benefits in patients with amplified MDM2 intimal sarcoma. Predictive biomarkers other than amplified MDM2 and acquired resistance mechanisms for milademetan are unknown. Whole-exome and RNA sequencing analyses of pre-treatment tissue samples were conducted to identify determinants of response. Genomic alterations were analyzed for 10 patients, and gene expression was analyzed for 9 patients using their pre-treatment tissue samples. Targeted sequencing of cell-free DNA (cfDNA) samples (liquid biopsy) was also conducted sequentially at three points [before treatment with milademetan (baseline), at Cycle 2 Day1, and at the time of disease progression] to identify determinants of response and resistance. From whole-exome and RNA sequencing analyses of pre-treatment tissue samples, we could not find any molecular pathways associated with the anti-tumor activity of milademetan. Focusing on 8 genes (CDK4, CDKN2A, CDKN2B, EGFR, ERBB3, MDM2, PDGFRA, TP53) known to be frequently affected in intimal sarcoma and 10 genes (AKT1, ATM, BBC3, CDKN1A, CDKN1C, CHEK2, MDM4, PMAIP1, PPM1D, TWIST1) reported to be associated with MDM2 inhibitor responses; we found that anti-tumor activity correlated with amplified TWIST1 (p-value = 0.028) and negatively with CDKN2A loss (p-value = 0.071). Eight of the 10 patients had their cfDNA collected sequentially at baseline, at Cycle 2 Day1 and disease progression; however, one did not consent to the exploratory analysis study using cfDNA, and one had cfDNA collected at baseline but not at disease progression due to ongoing treatment. Of the eight patients, TP53 mutations in cfDNA were detected in one and five patients at baseline and disease progression, respectively. The cfDNA allele frequency of TP53 mutations increased with disease progression. CDKN2A loss and amplified TWIST1 could be associated with the anti-tumor activity of milademetan in patients with MDM2 amplified intimal sarcoma. Acquired TP53 mutations were detected in sequential liquid biopsies as loss-of-function mutations, and these TP53 mutations might compromise the anti-tumor activity.

  Study JGAS000619

• Whole Exome Characterization of Squamous Cell Lung Cancers (Lung SQCC) from Appalachian Kentucky (APPKY)

  This is a pilot study of squamous cell lung cancer and matched normal tissue pairs collected (convenience sample) from patients from Central Appalachia, in Southeastern Kentucky. This study performed whole exome sequencing on tumor and matched normal DNA samples from 51 lung squamous cell carcinoma (SQCC) subjects from Appalachian Kentucky (AppKY). Somatic genomic alteration profiles were compared between the AppKY and TCGA SQCC cohorts. We found that IDH1 and PCMTD1 had higher mutation rates in AppKY versus TCGA. These findings suggest population differences in the genetics of lung SQCC between AppKY and US populations that have implications for personalized treatment for this disease.

  Study phs001651

• Development of Novel Histiocytic Sarcoma Organoid Model for Drug Discovery

  Histiocytic sarcoma is an extremely rare and aggressive hematopoietic malignancy. Its pathogenesis remains poorly understood and effective treatments are lacking. We treated a patient with histiocytic sarcoma of soft tissue in Osaka International Cancer Institute and established an organoid culture from a resected tumor specimen using a modified air���liquid interface method. After serial passaging, the organoid was successfully xenografted into NOD-scid IL2Rgnull (NSG) mice. The established organoid retained key histological features and genetic characteristics of the original tumor. This organoid model offers a novel and reliable platform for studying the biology of histiocytic sarcoma and may contribute to the development of future therapeutic strategies.

  Study JGAS000807

• Evolution of GBM through therapy

  Primary glioblastoma (GBM) tumours recur following treatment. This is likely due to intratumour heterogeneity (ITH), which reduces the effectiveness of cancer therapies by enabling therapy-driven tumour evolution: Darwinian selection of genotypically and/or phenotypically distinct cells (subclones) that resist treatment to seed regrowth of an even less treatable recurrence. To investigate this we sequenced a pilot cohort of nine paired primary and locally recurrent GBM tumours, alongside matched blood samples, in order to begin characterising therapy resistant cells and thereby infer the mechanisms by which they evaded treatment. These data were included in the first data release from the Glioma Longitudinal AnalySiS (GLASS) consortium.

  Study EGAS00001003546

• CONSERTING: integrating copy number analysis with structural variation detection

  We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), a novel algorithm for detecting somatic copy number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation by read depth change and localized structural variation detection to achieve high accuracy and sensitivity. Analysis of 43 pediatric and adult cancer genomes revealed novel oncogenic CNAs, complex re-arrangements and subclonal CNAs missed by alternative approaches. This study contains all data for "CONSERTING: an accurate method for detecting somatic DNA copy number alterations in whole genome sequencing data", which was previously split between EGAS00001001202 and EGAS00001001050.

  Study EGAS00001001202

• Genome-wide genetic and epigenetic dataset of pancreatic acinar cell carcinomas

  Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. To identify potential targets for personalized treatment, integrative genome- and epigenome-wide analyses were performed. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are known. The tumor suppressors ID3, ARID1A, APC, and CDKN2A are frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis. Consequently, this work identifies potential novel therapeutic targets in ACC for drugs recently approved for precision cancer therapy.

  Study EGAS00001002533

• Exome-wide somatic mutation characterization of small bowel adenocarcinoma

  Small intestinal adenocarcinoma (SIA) is a rare and aggressive form of cancer with limited treatment options. To further characterize the somatic mutation landscape of this tumor type, exome sequencing was conducted on a population-based set of SIA samples from all three parts of the small intestine. Archival tissue from 106 tumors with comprehensive clinical patient information entered exome sequencing from a patient series consisting of SIA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify significantly mutated genes from the exome data. Also mutational signature and pathway enrichment analyses were performed.

  Study EGAS00001002559

• Genome Landscape of Primary Pancreatic Ductal Adenocarcinoma

  The purpose of the Australian ICGC Pancreatic Cancer Genome Sequencing Initiativestudy is to identify the common driving mutations underlying the initiation anddevelopment of Pancreatic Adenocarcinoma in a large cohort of pancreatic cancerpatients (n=350). Matched genome sequences will be generated from normal tissue(duodenum) and resected primary tumour tissue in each patient using exome andwhole genome sequencing. The complete repertoire of somatic mutations will bedetermined (substitutions, indels, copy number changes and structural changes).Where possible, matched transcriptome sequencing will also be carried out todetermine locus activity, which mutations are actively expressed and whichrearrangements give rise to gene-fusion transcripts.

  Study EGAS00001000154

• Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocarcinogenesis

  Infection by Hepatitis B Virus (HBV) is the main risk factor for Hepatocellular Carcinoma (HCC) worldwide. HBV can directly drive carcinogenesis through integrations in human genome. This integrative analysis of a French cohort of 190 patients mainly coming from Europe and Africa provides a deep characterization of HBV integrations, in relation with viral and host genomics and clinical features. Clonal HBV integrations directly contribute to HCC development through alterations of cancer driver genes, either at distance when co-localizing with copy number alterations, either locally through viral Enhancers. Together, this analysis gives new insights on HBV-associated driver mechanisms involved in hepato-carcinogenesis.

  Study EGAS00001004629

• Deciphering somatic mosaic structural variation in human blood lineages using single-cell multiomics

  Somatic mosaicism (SM), referring to the presence of somatic mutations in sub-populations of cells within healthy individuals, is associated with an increased risk of a variety of diseases, including cancer. Blood is at particularly high risk of SM, given its rapid turnover and functionally- heterogeneous cell-type composition. While the roles of point mutations and large-scale rearrangements in blood SM have been scrutinised in recent years, the functional impact of mosaic structural variants (mSVs) remains poorly understood. Using haplotype-resolved single-cell multi-omics, we explored the mSV landscape of human hematopoietic stem and progenitor cells (HSPCs).

  Study EGAS00001006567

• Single-cell transcriptomics identifies pathogenic T-helper 17.1 cells and pro-inflammatory monocytes in ICI-related pneumonitis

  ICI-pneumonitis is a frequent serious adverse event of cancer immunotherapy hinging on a cell-mediated immune response, though the exact pathophysiology is currently unknown. Using single-cell transcriptomics, an enrichment of pathogenic (TBX21, RORC, IFNG, IL17A, CSF2 expressing) T-helper 17.1 cells and pro-inflammatory (TNF, IL1B, IL6, IL23A expressing) monocytes was identified in ICI-pneumonitis bronchoalveolar lavage fluid, putatively engaging in a feedforward inflammatory loop. This finding yields several novel therapeutic targets for the treatment of ICI-pneumonitis. Most notably repurposing anti-IL-23 merits further research as a potential efficacious and safe treatment for ICI-pneumonitis.

  Study EGAS00001006762

• The landscape of somatic mutation in normal colorectal epithelial cells

  The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic events and consequent clonal expansions leading to cancer. As for most cancer types, however, understanding of the earliest phases of colorectal neoplastic change, which may occur in morphologically normal tissue, is comparatively limited because of the difficulty of detecting somatic mutations in normal cells. Each colorectal crypt is a small clone of cells derived from a single recently-existing stem cell. Here, we sequenced hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed, some ubiquitous and continuous, others only found in some individuals, in some crypts or during some phases of the cell lineage from zygote to adult cell. Likely driver mutations were present in ~1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium.

  Dataset EGAD00001004192

• August 2021 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  August 2021 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001008101

• MutWP5: CRUK Mutographs of Cancer: Lung: PD43291_Novaseq (WG)

  Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutaiton burden in different portions of the lung. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this poriton of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs. . This dataset contains all the data available for this study on 2023-03-08.

  Dataset EGAD00001010111

• Spatially resolved antigen receptor and gene expression data from breast cancer patients

  The dataset includes spatially-resolved and single-cell antigen receptor, as well as gene expression, data from two different HER2+ breast cancer patients. The tumor piece obtained during surgery from each patient was divided into several regions and tissue sections were used for spatial transcriptomics (Visium, 10x genomics). As indicated, some tissue sections were analyzed by a new method (Spatial VDJ) to spatially resolve antigen receptor sequences (target capture), which was developed in our publication. In parallel, tissue pieces from the same tumor were dissociated for single-cell gene expression analysis (10x genomics GEX, VDJ, and feature barcoding/Hash Tag Oligonucleotide). The deposited data is in the form of fastq files. All processed data, metadata, micrographs of the tissue sections (of those used for spatial transcriptomics), and scripts used for the analysis are publicly available at Zenodo (DOI: 10.5281/zenodo.7961605). Final libraries were sequenced on NextSeq2000 (Illumina) or NovaSeq6000 (Illumina) and analyzed with Cell Ranger, Seurat, Space Ranger, and STutility pipelines.

  Dataset EGAD00001011061

• Geographic variation of mutagenic exposures in kidney cancer genomes – filtered vcf files (Mutographs)

  Geographic variation of mutagenic exposures in kidney cancer genomes – filtered vcf files (Mutographs)

  Dataset EGAD00001012222

• Geographic variation of mutagenic exposures in kidney cancer genomes – patient metadata files (Mutographs)

  Geographic variation of mutagenic exposures in kidney cancer genomes – patient metadata files (Mutographs)

  Dataset EGAD00001012223

• Geographic variation of mutagenic exposures in kidney cancer genomes – structural variation vcf files (Mutographs)

  Geographic variation of mutagenic exposures in kidney cancer genomes – structural variation vcf files ( Mutographs )

  Dataset EGAD00001013726

• Geographic variation of mutagenic exposures in kidney cancer genomes – copy number variants (Mutographs)

  Geographic variation of mutagenic exposures in kidney cancer genomes – copy number variants (Mutographs)

  Dataset EGAD00001013727

• Jackson Heart Study (JHS) Cohort

  The Jackson Heart Study (JHS) is a large, community-based, observational study whose participants were recruited from urban and rural areas of the three counties (Hinds, Madison and Rankin) that make up the Jackson, MS metropolitan statistical area (MSA). Participants were enrolled from each of 4 recruitment pools: (1) random, 17%, (2) volunteer, 30%, (3) currently enrolled in the Atherosclerosis Risk in Communities (ARIC) Study, 31%, and (4) secondary family members, 22%. The final cohort of 5,306 participants included 6.59% of all African American Jackson MSA residents, aged 35-84, during the baseline exam (N-76,426, US Census 2000). Among these, approximately 3,600 gave consent that allows genetic research and deposition of data into dbGaP. Major components of three clinic examinations (see study history) include medical history, physical examination, blood/urine analytes, and interview questions on areas such as physical activity, stress, coping and spirituality, racism and discrimination, socioeconomic position, and access to health care. Extensive clinical phenotyping includes anthropometrics, electrocardiography, carotid ultrasound, ankle-brachial blood pressure index, echocardiography, CT chest and abdomen for coronary and aortic calcification, liver fat, and subcutaneous and visceral fat measurements, and cardiac MRI. At 12-month intervals after the baseline clinic visit (Exam 1), participants have been contacted by telephone to update information, confirm vital statistics, document interim medical events, hospitalizations and functional status, and obtain additional sociocultural information. Questions about medical events, symptoms of cardiovascular disease and functional status are repeated annually. Ongoing cohort surveillance includes abstraction of medical records and death certificates for relevant International Classification of Diseases (ICD) codes and adjudication of nonfatal events and deaths. CMS data are currently being incorporated into the dataset. Note: Regarding date variables warehoused in the Jackson Heart Study (JHS) Cohort on dbGaP, the coordinating center has developed an algorithm that will systematically review and de-identify any of the (nearly 100) date-related variable types stored in the data package. To simultaneously minimize (i) de-identifiability of the data and (ii) impact on analyses utilizing sensitive data elements, a participant-level random number was generated to avoid the necessity of sharing any potentially sensitive data. The coordinating center maintains an archived linkage of these data in their raw form and regularly reviews ad hoc requests to utilize the raw data on a project-by-project basis. The JHS Cohort is utilized in the following dbGaP substudies. To view genotypes, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" section of this top-level study page phs000286 JHS Cohort. phs000402 ESP Heart GO JHS phs000498 JHS Allelic Spectrum Seq phs000499 JHS CARephs001069 MI Gen JHS phs001098 T2D GENES Exome Seq phs001356 Exome Chip phs002256 Cardiometabolic Renal Proteomics phs002369 Metabolomics Insulin Resistance

  Study phs000286

• RNAseq dataset for MALT1 in MCL

  Manuscript Title: Co-targeting of BTK and MALT1 overcomes resistance to BTK inhibitors in mantle cell lymphoma Journal: Journal of Clinical Investigation Authors Vivian Changying Jiang1, Yang Liu1, Junwei Lian1, Shengjian Huang1, Alexa Jordan1, Qingsong Cai1, Fangfang Yan3, Joseph Mitchell McIntosh1, Yijing Li1, Yuxuan Che1, Zhihong Chen1, Jovanny Vargas1, Maria Badillo1, JohnNelson Bigcal1, Heng-Huan Lee1, Wei Wang1, Yixin Yao1, Lei Nie1, Christopher Flowers1, and Michael Wang1, 2* Abstract Bruton’s tyrosine kinase (BTK) is a proven target in mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma. However, resistance to BTK inhibitors is a major clinical challenge. We here report that MALT1 is one of the top overexpressed genes in ibrutinib-resistant MCL cells, while expression of CARD11, which is upstream of MALT1, is decreased. MALT1 genetic knockout or inhibition produced dramatic defects in MCL cell growth regardless of ibrutinib sensitivity. Conversely, CARD11 knockout cells showed anti-tumor effects only in ibrutinib-sensitive cells, suggesting that MALT1 overexpression could drive ibrutinib resistance via bypassing BTK-CARD11 signaling. Additionally, BTK knockdown and MALT1 knockout markedly impaired MCL tumor migration and dissemination, and MALT1 pharmacological inhibition decreased MCL cell viability, adhesion, and migration by suppressing NF-κB, PI3K-ATK-mTOR, and integrin signaling. Importantly, co-targeting MALT1 with safimaltib and BTK with pirtobrutinib induced potent anti-MCL activity in ibrutinib-resistant MCL cell lines and patient-derived xenografts. Therefore, we conclude that MALT1 overexpression associates with resistance to BTK inhibitors in MCL, targeting abnormal MALT1 activity could be a promising therapeutic strategy to overcome BTK inhibitor resistance, and co-targeting of MALT1 and BTK should improve MCL treatment efficacy and durability as well as patient outcomes. Dataset description: The bulk RNA-seq dataset was generated for the cell lines below and used for two major purposes: 1. DEG analysis and GSEA analysis comparing IBN-R and IBN-S cells 2. DEG analysis and GSEA analysis comparing MCL cells with/without MI-2 treatment. sample Cell MI-2 Ibrutinib (IBN) Venetoclax (VEN) Used for IBN-R vs IBN-S comparison Used for MI-2 vs untreated (DMSO) H9 Granta519 - R S yes H21 Granta519 - R S yes H33 Granta519 - R S yes H10 Granta519-VEN-R - R R yes H22 Granta519-VEN-R - R R yes H34 Granta519-VEN-R - R R yes H3 JeKo BTK KD_1 - R R yes yes H15 JeKo BTK KD_1 - R R yes yes H27 JeKo BTK KD_1 - R R yes yes H5 JeKo BTK KD_2 - R R yes yes H17 JeKo BTK KD_2 - R R yes yes H29 JeKo BTK KD_2 - R R yes yes H1 JeKo-1 - S R yes yes H13 JeKo-1 - S R yes yes H25 JeKo-1 - S R yes yes H7 Mino - S S yes H19 Mino - S S yes H31 Mino - S S yes H8 Mino-VEN-R - S R yes H20 Mino-VEN-R - S R yes H32 Mino-VEN-R - S R yes H11 Rec-1 - S S yes H23 Rec-1 - S S yes H12 Rec-VEN-R - S S yes H24 Rec-VEN-R - S R yes H36 Rec-VEN-R - S R yes H35 Rec-1 -- S R yes H4 JeKo BTK KD_1 + MI-2 + yes H16 JeKo BTK KD_1 + MI-2 + yes H28 JeKo BTK KD_1 + MI-2 + yes H6 JeKo BTK KD_2 + MI-2 + yes H18 JeKo BTK KD_2 + MI-2 + yes H30 JeKo BTK KD_2 + MI-2 + yes H2 JeKo-1 + MI-2 + yes H14 JeKo-1 + MI-2 + yes H26 JeKo-1 + MI-2 + yes

  Dataset EGAD00001009771

• TNF-induced dynamic regulation of mRNA stabilome in rheumatoid arthritis fibroblast-like synoviocytes

  During rheumatoid arthritis (RA), TNF activates fibroblast-like synoviocytes (FLS) inducing in a temporal order a constellation of genes, which perpetuate synovial inflammation. Although the molecular mechanisms regulating TNF-induced transcription are well characterized, little is known about the impact of mRNA stability on gene expression and the impact of TNF on decay rates of mRNA transcripts in FLS. To address these issues we performed RNA sequencing and genome-wide analysis of the mRNA stabilome in RA FLS. We found that TNF induces a biphasic gene expression program: initially, the inducible transcriptome consists primarily of unstable transcripts but progressively switches and becomes dominated by very stable transcripts. This temporal switch is due to: a) TNF-induced prolonged stabilization of previously unstable transcripts that enables progressive transcript accumulation over days and b) sustained expression and late induction of very stable transcripts. TNF- induced mRNA stabilization in RA FLS occurs during the late phase of TNF response, is MAPK-dependent, and involves several genes with pathogenic potential such as IL6, CXCL1, CXCL3, CXCL8/IL8, CCL2, and PTGS2. These results provide the first insights into genome-wide regulation of mRNA stability in RA FLS and highlight the potential contribution of dynamic regulation of the mRNA stabilome by TNF to chronic synovitis.

  Study phs001371

• Identification and Targeting of Inflammatory Macrophage-Fibroblast Crosstalk in Rheumatoid Arthritis

  Macrophages tailor their function according to the signals found in tissue microenvironments, assuming a wide spectrum of phenotypes. A detailed understanding of macrophage phenotypes in human tissues is limited. Using single-cell RNA sequencing, we defined distinct macrophage subsets in the joints of patients with the autoimmune disease rheumatoid arthritis (RA), which affects ~1% of the population. The subset we refer to as HBEGF+ inflammatory macrophages is enriched in RA tissues and is shaped by resident fibroblasts and the cytokine tumor necrosis factor (TNF). These macrophages promoted fibroblast invasiveness in an epidermal growth factor receptor-dependent manner, indicating that intercellular cross-talk in this inflamed setting reshapes both cell types and contributes to fibroblast-mediated joint destruction. In an ex vivo synovial tissue assay, most medications used to treat RA patients targeted HBEGF+ inflammatory macrophages; however, in some cases, redirecting them into a state is not expected to resolve inflammation. These data highlight how advances in our understanding of chronically inflamed human tissues and the effects of medications therein can be achieved by studies on local macrophage phenotypes and intercellular interactions. Reprinted from Kuo, Ding et al., Science Translational Medicine 2019, PMID: 31068444, with permission from American Association for the Advancement of Science.

  Study phs001340