3794 results for "*oma"

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• Meta-Analysis of Genome-Wide Association Studies of Bladder Cancer Risk

  This meta-analysis consists of genome-wide genotype for 13,447 cases and 342,580 controls of European ancestry to identify novel susceptibility loci for bladder cancer. Cases were defined as histologically confirmed primary carcinoma of the urinary bladder of all stages, including carcinoma in situ (International Classification of Diseases for Oncology, C670-C679, 188). All histologic subtypes were included. Summary-level results for the association between genotyped/imputed variants and risk of bladder cancer are included.

  Study phs003342

• Single-Cell Transcriptomics of Adult Recurrent Respiratory Papillomatosis

  These single-cell sequencing data were generated from diseased respiratory tract papilloma tissue caused by chronic infection with HPV 6 or 11. Patients from which this tissue was derived participated in a phase I clinical trial using a novel therapeutic vaccine, but these samples were acquired before this experimental treatment. The aim of performing this single-cell sequencing study was to characterize the papilloma cells and other cells in the papilloma microenvironment with single-cell analyses using the 10X Genomics platform. The single-cell gene expression raw data files for each sample will be available in this submission.

  Study phs003349

• Non-Coding Mutations Cause Enhancer Targeting Resulting in Protein Synthesis Dysregulation During B-Cell Lymphoma Progression

  In this study, we performed whole-genome sequencing of longitudinal tumor pairs, representing transformation of follicular lymphoma (FL) to high grade B-cell lymphoma with MYC and BCL2 rearrangements (known as "double hit lymphoma" or DHL), a very aggressive class of non-Hodgkin B cell lymphoma (B-NHL). We identified coding and noncoding genomic alterations acquired during the course of lymphoma progression.

  Study phs003398

• 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

• A Phase III Randomized Study of Nivolumab Plus Ipilimumab Versus Nivolumab in Stage IV Squamous Cell Lung Cancer

  Lung-MAP (S1400, NCT02785952) was a multicenter, open-label, phase III randomized clinical trial. The Lung-MAP-I substudy (S1400I) was conducted from December 2015 to April 2018, through the National Clinical Trials Network and led by the SWOG Cancer Research Network. The trial compared nivolumab plus ipilimumab (nivo+ipi) with nivolumab monotherapy (nivo) in patients with chemotherapy-pretreated, immunotherapy-naïve, advanced squamous non-small cell lung carcinoma (sqNSCLC). Two hundred fifty-two patients were randomly assigned to receive nivo+ipi (n = 125) or nivo (n = 127). The clinical efficacy endpoints were overall survival, progression free survival, duration of response, and best objective response by RECIST 1.1. Multi-omic translational analysis was performed in collaboration with the the CIMAC–Cancer Immunologic Data Commons (CIDC) Network using available tumor tissue samples and blood samples (n = 160) submitted for Lung-MAP screening and provided by the SWOG tissue bank.

  Study phs003412

• Resistance Development in Basal Cell Nevus Syndrome through the Basal to Squamous Transition

  While basal cell carcinomas (BCCs) arise from ectopic hedgehog pathway activation and can be treated with pathway inhibitors, sporadic BCCs display high resistance rates, while tumors arising in Gorlin syndrome patients with germline Patched (PTCH1) mutations are uniformly suppressed by inhibitor therapy. In rare cases, Gorlin syndrome patients on long-term inhibitor therapy will develop individual resistant tumor clones that rapidly progress, but the basis of this resistance remains unstudied. Here we report a case of a Smoothened inhibitor (SMOi)-resistant tumor arising in a Gorlin patient on suppressive SMOi for nearly a decade. Using a combination of multi-omics and spatial transcriptomics, we define the tumor populations at the cellular and tissue level to conclude that Gorlin tumors can develop resistance to SMOi through the previously described basal to squamous cell carcinoma transition (BST). Intriguingly, through spatial whole exome genomic analysis, we nominate PCYT2, ETNK1, and the phosphatidylethanolamine biosynthetic pathway as novel genetic suppressors of BST resistance. These observations provide a general framework for studying tumor evolution and provide important clinical insight into mechanisms of resistance to SMOi for not only Gorlin syndrome but sporadic BCCs as well.

  Study phs003415

• CALGB/SWOG 80405: Genome-Wide Association Study of Patients with Advanced or Metastatic Colorectal Cancer Treated with First-Line Chemotherapy Combined with Cetuximab and/or Bevacizumab

  CALGB/SWOG 80405 (NCT00265850) was a randomized phase III study of bevacizumab, cetuximab, or the combination of these two monoclonal antibodies, in addition to systemic chemotherapy for patients with untreated metastatic adenocarcinoma of the colon or rectum. We prospectively collected germline DNA and conducted genome-wide association studies using clinical outcomes and molecular features.

  Study phs003428

• Circulating Genomic Determinants of Treatment Failure in Hodgkin Lymphoma

  In this study, we show that the plasma representation of mutations exceeds the bulk tumor representation in most cases, making classic Hodgkin Lymphoma (cHL) particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumors, we demonstrate hazard ratios (HRs) circulating tumor DNA (ctDNA) shedding to be shaped by DNASE1L3, whose increased tumor microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R-mutations that are dependent on IL13 signaling and therapeutically targetable with IL4R blocking antibodies. Finally, we demonstrate the clinical value of pre- and on-treatment ctDNA levels for longitudinally refining cHL risk prediction, and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL as well as capturing molecularly distinct subtypes with diagnostic, prognostic, and therapeutic potential.Methods utilized include a) targeted genotyping of baseline plasma samples, b) whole exome sequencing (WES) of baseline plasma samples, c) epigenetic expression inference from cell-free DNA-sequencing (EPIC-Seq) to infer gene expression from cell-free DNA (cfDNA) fragmentation profiles, d) ctDNA tracking in on-treatment samples, e) RNA-Sequencing, and f) Phased variant Enrichment and Detection Sequencing (PhasED-Seq).All patients were treated at cancer centers across Europe and North America between 2011 and 2020. The following 3 cancer centers, Stanford (CA, USA), Bellinzona [Confoederatio Helvetica (CH) or Switzerland], and Leuven (Belgium), were included. The 6 clinical trial collectives included in this study are the Phase III trial AHOD1331 trial (NCT02166463) and the Phase II cHOD17 study (NCT03755804) for enrolled pediatric patients, the Phase III AHL2011 (NCT01358747), the Phase II BREACH trial (NCT02292979), a pilot study evaluating concurrent Pembrolizumab with AVD (Doxorubicin, also known as Adriamycin, Vinblastine, and Dacarbazine; NCT03331341), and a Phase II study evaluating PVAB (Prednisone, Vinblastine, Doxorubicin and Bendamustine; NCT02414568) in older patients (61 years and older). In addition, lymph node specimens from a biorepository at St. Jude Children's Research Hospital (TN, USA) were included.

  Study phs003435

• KRT17High/CXCL8+ Tumor Cells Display Both Classical and Basal Features and Regulate Myeloid Infiltration in the Pancreatic Cancer Microenvironment

  Recent studies have uncovered the co-existence of basal and classical subtypes within pancreatic ductal adenocarcinoma (PDAC). We sought to characterize these intermediary cells using single-cell RNA sequencing of PDAC. We performed subtyping on 18 single-cell RNA sequencing human PDAC samples to identify multiple intermediary subtypes. We compared single-cell profiling of patient-matched blood and tumor samples to measure changes in the local and systemic immune microenvironments in CXCL8-high tumors vs. CXCL8-low tumors. Finally, we leveraged longitudinally patient-matched blood over the course of chemotherapy. In our studies we identified a cluster of KRT17high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines which in turn influence the myeloid compartment both locally and systemically. We utilized sequencing data from dbGaP study accession phs002070. In addition to that, we included sequencing from new specimens which are deposited to this submission, consisting of one additional tumor specimen and 5 PBMC samples, sequenced after chemotherapy (longitudinally matched to PBMC samples in phs002071.v1.p1). FASTQ files of these sequencing runs are available through this dbGaP submission.

  Study phs003436

• Profiling RNA Translation in Pediatric Medulloblastoma

  This study provides RNA-sequencing and ribosome profiling data for patient-derived cell lines and patient tissue samples for children with medulloblastoma. Ribosome profiling is a variant protocol of RNA-sequencing that directly sequences ribosome-bound RNA fragments only. Associated RNA-seq and Ribo-seq data obtained separately for some cancer cell lines can be found on the NCBI SRA as PRJNA957428. Samples were processed for poly-A mRNA sequencing using the Roche Kapa Kit. Ribosome profiling was performed as described in the manuscript referenced below (Hofman et al.) and based on the article by McGlincy et al., Methods (2017). Ribo-seq data were analyzed for sample quality using RiboseQC (Calviello, Nat Struct Mol Biol, 2020). These data were used to quantify P-sites of open reading frames. RNAseq and ribo-seq data were integrated and compared to determine translational efficiency values using TPM (Ribo-seq) over TPM (RNA-seq) as the metric. Ribo-seq data on 14 samples and RNAseq data on 21 samples derived from 16 fresh-frozen surgical samples for medulloblastoma and 5 autopsy samples are available through dbGaP. A second cohort of 4 medulloblastoma samples (RNAseq, Ribo-seq) related to this study can be found on the EGA at EGAS00001007426.

  Study phs003446

• MAESTRO-Pool Enables Highly Parallel and Specific Mutation-Enrichment Sequencing for Minimal Residual Disease Detection in Cohort Studies

  MAESTRO-Pool builds upon the technology MAESTRO (Minor Allele Enriched Sequencing Through Recognition Oligonucleotides) by pooling tumor-specific MAESTRO probes from multiple patients and applying these to all samples from all patients. In this study, MAESTRO-Pool was applied to a cohort of 9 melanoma patients where 98 plasma samples were screened for 22,333 mutations. Additionally, a new dynamic minimal residual disease (MRD) caller was used to estimate the likelihood of MRD detection based on the number mutations and cell-free DNA molecules interrogated which allowed each bespoke MRD test to be properly calibrated against false detection. These developments led to sensitive detection in patient-matched samples down to 0.78 parts per million (ppm) while limiting false detection in negative controls to 1/784 (tumor fraction=2.7 ppm). MAESTRO-Pool and the dynamic MRD caller enable a unique blend of sensitivity, specificity, and efficiency, which will improve the ability to detect MRD.The data contained in this repository consists of:Tumor and normal whole genome sequencing data used to call patient-specific tumor mutations and design the MRD Tracker and MAESTRO-Pool fingerprintsMAESTRO-Pool data (enriched duplex sequencing via hybrid capture) of tumor gDNA, normal gDNA and cfDNA MRD Tracker data (duplex sequencing via hybrid capture) of tumor gDNA, normal gDNA and cfDNA

  Study phs003447

• BPH Tissues for Cell Culture and Analysis - Spatial Transcriptomics Identifies Candidate Stromal Drivers of Benign Prostatic Hyperplasia

  The study goal was to apply spatial transcriptomics to identify candidate stromal drivers of benign prostatic hyperplasia (BPH). Laser microdissection (LCM) with RNA-seq of the stroma adjacent to hyperplastic and budding BPH ducts identified secreted factors including IGF1 and CXCL13. Single‐cell RNA sequencing (scRNA‐seq) revealed their co-expression from BPH fibroblasts. Additional studies sought to define similarities to embryonic prostate development, as well as therapeutic applications. Subjects were those who underwent prostatectomy for prostate or bladder cancer, with concurrent BPH, and who consented to use of surplus tissue for research studies. LCM/RNA-seq studies included 5 patients, and scRNA-seq studies included 1 patient. Phenotypic data submitted to this study include patient age, sex, prostate size, and international prostate symptom score (IPSS). Sequencing was done on an Illumina NovaSeq 6000 (LCM/RNAseq) and Illumina HiSeq X-Ten (scRNA-seq). The data processing pipeline utilized Kallisto (LCM/RNA-seq) and Cell Ranger (scRNA-seq). Data submitted are raw sequencing (Fastq) files.

  Study phs003477

• A Missense SNP in the Tumor Suppressor SETD2 Reduces H3K36me3 and Mitotic Spindle Integrity in Drosophila

  While examining DNA from renal cell carcinoma (RCC) patients we observed a single nucleotide polymorphism (SNP; rs58906143,chr3:47163422 C→G (hg19); E902Q*) within SETD2 that was overrepresented in kidney cancer patients compared to control patients. This original study utilized directed sequencing of 14 genes. In an expanded study using a Taqman assay to study the specific SNP, a G allele was found in 72/493 cases (14.6%) and 24/356 (6.7%) controls. Analysis by ancestry revealed that there was there was a G allele in 50/119 (42.0%) cases and 21/71 (29.6%) controls in patients with African Ancestry while there was a G allele in 19/335 cases (5.7%) and 3/269 (1.1%) controls in patients with European Ancestry. These differences did not reach statistical significance. Concurrently, we studied the functional effect of this SNP in a Drosophila model. The homologous amino acid substitution at E741Q reduces H3K36me3 levels which could be rescued by wild type Set2. Additionally, the mutation resulted in significant defects in spindle morphogenesis, consistent with a role for SETD2 in alpha-tubulin methylation during mitosis. Data available through dbGAP include the 14 gene sequence files of 52 control and 128 RCC patients, the results of Taqman SNP (rs58906143) analysis in text files for 221 controls and 357 RCC patients, and compiled phenotype data including age and assigned race. Due to data use limitations, genotyping data for 8 RCC patients and 83 controls as well as GWAS data for ancestry determination will not be available on dbGaP, but will be made available on request.

  Study phs003474

• Germline Genome Sequencing from Patients with Early-Onset Merkel Cell Carcinoma

  Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer associated with advanced age. Approximately 5% of cases are early-onset MCC, occurring in individuals younger than 50 years. This study used genome sequencing to identify germline risk factors among patients with early-onset MCC. The available data in the database of Genotypes and Phenotypes (dbGaP) includes genome sequencing of peripheral blood mononuclear cell (PBMC) DNA from 37 patients with early-onset MCC (age ATM = 2, BRCA1 = 2, BRCA2 = 1, TP53 = 1, and MAGT1 = 1).

  Study phs003485

• Spatial Transcriptomics Reveals Discrete Tumor Microenvironments and Autocrine Loops Within Ovarian Cancer Subclones

  Ovarian masses from patients with high grade serous ovarian carcinoma undergoing debulking surgery were subjected to spatial transcriptomics profiling using the 10x Genomics Visium (fresh frozen) platform. Copy number inference using inferCNV predicted the presence of subclones with mutually exclusive copy number alterations (CNAs) in 5 of the 8 patient samples studied. In one patient, 3 subclones were predicted. For this patient sample, a serial section of the same tumor was used to microdissect regions corresponding to each of these subclones, and a 'normal' region predicted to contain only fibroblasts and no tumor cells. These microdissected regions were processed for low pass whole genome sequencing (WGS) and CNAs recorded using ichorCNA. An oral biopsy lacking tumor cells from an unrelated donor was used as a negative control for CNA inference. The CNAs predicted by inferCNV for the three subclones were validated by the low pass WGS and no CNAs were observed in the normal region containing fibroblasts.

  Study phs003561

• Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups

  Study EGAS00001006402

• Gene expression profiling of HGCC patient-derived Glioblastoma Cell Lines (ISPA-GBM)

  Study EGAS00001006814

• Mechanisms of duodenal adenoma development in familial polyposis syndromes

  Study EGAS00001006561

• UAMS - Myeloma Institute Data Access Committee

  Dac EGAC00001000845

• MD Anderson Lymphoma & Myeloma Data Access Committee

  Dac EGAC00001002706

• Unraveling the genetics of transformed splenic marginal zone lymphoma

  Study EGAS00001006389

• Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome

  Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP.  This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported.

  Study EGAS00001007937

• Total RNA-Sequencing of patient-derived xenograft models of myxoid liposarcoma

  Study EGAS00001004901

• Loss of SDHB promotes dysregulated iron homeostasis, oxidative stress and sensitivity to ascorbate

  Succinate dehydrogenase is a key enzyme in the tricarboxylic acid cycle and the electron transport chain. All four subunits of succinate dehydrogenase are tumor suppressor genes predisposing to paraganglioma, but only mutations in the SDHB subunit are associated with increased risk of metastasis. Here we generated an Sdhd knockout chromaffin cell line and compared it to Sdhb-deficient cells. Both cell types exhibited similar SDH loss of function, metabolic adaptation, and succinate accumulation. In contrast, Sdhb-/- cells showed hallmarks of mesenchymal transition associated with increased DNA hypermethylation and a stronger pseudo-hypoxic phenotype compared to Sdhd-/- cells. Loss of SDHB specifically led to increased oxidative stress associated with dysregulated iron and copper homeostasis in the absence of NRF2 activation. High-dose ascorbate exacerbated the increase in mitochondrial reactive oxygen species, leading to cell death in Sdhb-/- cells. These data establish a mechanism linking oxidative stress to iron homeostasis that specifically occurs in SDHB deficient cells and may promote metastasis. They also highlight high-dose ascorbate as a promising therapeutic strategy for SDHB-related cancers.

  Study EGAS00001005279

• Single cell multi-omics analysis of chromothriptic medulloblastoma highlights genomic and transcriptomic consequences of genome instability

  Study EGAS00001005410