525 results for "retinitis+pigmentosa+2017+surgery+blog+"my+twin+died+at+birth""

in 11.02 milliseconds.

• Evolutionary Origins of Recurrent Pancreatic Cancer

  Surgery is the only curative option for patients with Stage I/II pancreatic cancer, nonetheless most patients will recur after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer we performed whole exome or targeted sequencing of 10 resected primary cancers and their matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease develops from a monophyletic or polyphyletic origin, and this distinction has potential clinical relevance. In all patients, treatment induced genetic bottlenecks led to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding. In one patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings strongly advocate for routine post-treatment sampling in the management of recurrent pancreatic cancer.

  Study EGAS00001004097

• The KATHERINE study of adjuvant trastuzumab emtansine in HER2-positive breast cancer: analysis of patients with HER2-negative residual invasive disease on re-testing

  Following chemotherapy and human epidermal growth factor 2 (HER2)-targeted neoadjuvant therapy for HER2-positive early breast cancer, residual invasive breast cancer at surgery may be HER2-negative on retesting in some patients. We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the core biopsy with HER2-negative central testing on their corresponding surgical specimen. In the 70/845 (8.3%) patients with HER2-negative residual disease on retesting at surgery, there were 11 IDFS events in the 42 trastuzumab-treated patients (26.2%) and none in the 28 T-DM1-treated patients, suggesting that T-DM1 should not be withheld in this patient population.

  Study EGAS00001006037

• Drug development for pediatric cancers: the importance of patient' s genomic data re-use

  Cancer in children is uncommon and the overall prognosis for most pediatric cancers is good. However, while the combined survival rates have improved over the last decades, certain childhood malignancies, such as high-grade gliomas or metastatic sarcomas, still remain incurable in most patients. New strategies for targeting those devastating diseases are imperative, and patient genomic data can become a key asset in the process [1]. The Pediatric Cancer Genome Project’s datasets At EGA, we store over 500 datasets with sequencing data from pediatric cancer patients. A remarkable case is the datasets belonging to the Pediatric Cancer Genome Project (PCGP) from St. Jude Children’s Research Hospital–Washington University (Table 1 - EGAS list). PCGP is an ambitious effort to identify the mutations that drive childhood cancer and find new cures. Those datasets include 600 patients with complete tumor and normal genomes from 15 different tumor types. PCGP datasets have been an important resource for various studies that pooled genomic data from different public and in-house datasets to perform extensive genomic characterizations and publish comprehensive pan-cancer pediatric studies [2],[3]. Other interesting pediatric cancer datasets are from the Pediatric Brain Tumor Consortium, Sickkids or ICGC PedBrain project. How data reuse impacts drug development for pediatric cancers Recently, in October 2024, Nature Communications published a work led by the University of Michigan where authors used data from EGA (PCGP) check the table below as part of their strategy to pursue the identification of new tumor vulnerabilities susceptible to becoming novel therapeutic targets in diffuse midline glioma. Diffuse midline gliomas (DMG) are treatment-resistant and uniformly fatal pediatric brain tumors. The prognosis of this brainstem tumor is dismal with a median overall survival of 9–12 months from diagnosis. In this study, the authors first developed a lab model of the disease and reanalyzed data from the EGA to identify genes potentially linked to tumor severity. This approach revealed involvement of specific metabolic pathways, suggesting new possibilities for therapeutic intervention. In mice, the study shows that the use of statins can improve survival. For a brief overview of the underlying science, diffuse midline gliomas present intratumor heterogeneity with subpopulations of less-differentiated oligodendrocyte precursors and more differentiated astrocytes. Authors established in vitro models to recapitulate both phenotypes and identify metabolic programs in both subpopulations. To determine the clinical relevance, the authors re-used gene expression data from 76 DMG patients identifying a gene signature predicting decreased overall survival. After extensive metabolic characterization of subpopulations, authors defined strategies to target specific metabolic vulnerabilities. Pre-clinical experiments in mice using OXPHOS inhibitors and statins showed a reduction in tumor burden and increased overall survival [4]. In this scenario, the re-use of high-quality patient’s sequencing data appeared as an advantageous strategy to support the clinical relevance of in-vitro and pre-clinical findings. On the other hand, in rare conditions such as childhood cancer, the availability of public datasets and the possibility of pooling data from different sources can be the only way to obtain impactful results that lead to improvements for patients. References Davidoff, A. M. Pediatric Oncology. Seminars in pediatric surgery 19, 225–233 (2010). Gröbner, S. N. et al. The landscape of genomic alterations across childhood cancers. Nature 555, 321–327 (2018). Venu Thatikonda et al. Comprehensive analysis of mutational signatures reveals distinct patterns and molecular processes across 27 pediatric cancers. Nature Cancer 4, 276–289 (2023). Mbah, N. E. et al. Therapeutic targeting of differentiation-state dependent metabolic vulnerabilities in diffuse midline glioma. Nature Communications 15, (2024). Datasets and Studies ID Title Access Policy Year EGAD00001000134 Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma McGill-DKFZ Pediatric Brain Tumour Consortium 2016 EGAS0000100192 Somatic Histone H3 Mutations in Diffuse Intrinsic Pontine Gliomas and Non-Brainstem Paediatric Glioblastomas St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project 2017 EGAS00001000575 Whole genome sequencing and whole exome sequencing of DIPG tumors and matched normal tissue The hospital for sick children ("SickKids") 2016 EGAD00001000792 Exome sequencing reads of paediatric glioblastoma McGill-DKFZ Pediatric Brain Tumour Consortium 2016 EGAD00001002006 Whole genome sequencing of paediatric glioblastoma in the ICGC PedBrain project ICGC PedBrain project 2016

  Blog drug-development-for-pediatric-cancers

• Illumina HumanCoreExome genotyping data from the British Society for Surgery of the Hand Genetics of Dupuytren’s Disease consortium (BSSH-GODD consortium) collection

  Dupuytren's Disease (DD - OMIM126900) is the most common heritable disorder of connective tissue. It is a fibroproliferative disorder of the palmer fascia, causing flexion contractures of affected digits. DD affects men more commonly than women. DD is an archetypal complex disease, with multiple genetic and environmental factors affecting the final expression of the disease phenotype. The incidence increases with age, and the prevalence of DD is therefore increasing as the UK population ages. Half of all patients present before age 60. DD causes significant functional impairment, and severe contractures can lead to permanent disability. The mainstay of current treatment is surgery, but recurrence and complications are both high. For severe contractures, the only suitable treatment option is amputation. The direct costs to the NHS are high, and underestimate the true economic costs to society. We collected salivary samples from adults in the UK who have had surgery for DD. We have genotyped these samples using the Illumina HumanCoreExome Beadchips. https://research.ndorms.ox.ac.uk/public/dupuytrens/what-is-dupuytrens-disease/

  Study EGAS00001001206

• Whole exome sequencing data for patients with Bosma arhinia microphthalmia syndrome (BAMS)

  Whole exome sequencing data for patients with Bosma arhinia microphthalmia syndrome (BAMS). The dataset includes 21 samples from 7 families with BAMS; see Gordon et al, Nature Genetics, 2017.

  Dataset EGAD00001003130

• Mutation_burden_in_sun_exposed_eyelid__MSSE_

  Eyelid skin from blepharoplasty surgery will be collected from patients of different ethnic origin (Chinese, Malay, Indian and Caucasion) exposed to tropical sunshine. 2mm2 biopsies will be collected and DNA sequenced using a specific bait capture set and at high depth. The aim is to try and see if different mutations expand in different ethnic populations.

  Study EGAS00001002512

• Introducing Federated EGA Affiliates: a newly defined tier in the Federated EGA Network

  We're happy to announce that we are now accepting Affiliates in the Federated EGA Network! Federated EGA is a global network of repositories enabling secure discovery and access to sensitive human data. Currently, Federated EGA consists of Central EGA (CEGA), which serves the global community, and nine national Nodes that serve respective jurisdictions. Did you know that the Federated EGA (FEGA) has always envisioned a third tier within the network? This brings us to FEGA Affiliates, recently defined in the newly approved "Federated EGA Structure and Organisation" document. This new tier broadens the range of institutions or organisations that can become part of FEGA. Thus begins a new era for the network. What is a FEGA Affiliate? A FEGA Affiliate archives and serves controlled-access data within its own governance scope, while still participating in federated discovery through the EGA catalogue. Affiliates can be individual organisations or institutions, healthcare genomics initiatives, consortia of institutions, as well as project-specific consortia (national or international). In practical terms, a FEGA Affiliate: Hosts and safeguards the data it archives. Submits non-personal metadata to CEGA so studies are discoverable and can receive EGA accessions. Manages permissions and data access workflows for its datasets. Provides data access and/or distribution, along with support, to authorised users. Key takeaways about FEGA Affiliates FEGA is now organised into three tiers: CEGA, FEGA Nodes, and FEGA Affiliates. Affiliates archive data from their own organisation and/or selected partner institutions (for example, an international consortium). Affiliates make studies discoverable through the EGA catalogue by submitting non-personal metadata for accessioning. Access decisions and conditions are managed locally by the Affiliate (e.g. distribution or access in a trusted research environment). Are you considering whether your institution or project might be a good fit as a FEGA Affiliate? Would you like to learn more about this tier? We have published a blog post that addresses potential common questions, providing answers on this topic. You can read it here.

  Blog fega-affiliates

• Differential Gene Expression in Cryptorchid Testes

  Differential Gene Expression in Cryptorchid Testes Study uses whole-genome RNA profiling of testicular biopsies to determine a potential causative role of isolated congenital cryptorchidism in azoospermia and/or infertility in the context of our previously published GeneChip data. Cryptorchid patients, aged 7 months to 5 years and otherwise healthy, were enrolled in this prospective study. During surgery, testicular tissue biopsies were obtained for histological examination and RNA-sequencing (RNA-seq). Fifteen patients were selected based on the histological results and were divided into two groups. Seven were classified as belonging to the high infertility risk (HIR) and eight to the low infertility risk (LIR) group. Cryptorchid boys in the high infertility risk group lacked transformation of gonocytes into Ad spermatogonia due to impaired mini puberty. This group of patients will be infertile despite successful surgery.

  Study phs001275

• Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer: DNA Sequencing

  This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. All participants in this study were female. RNA sequencing data from the same patients were published under phs001863. Subject aliases are the same in the two datasets.

  Study phs003801

• Expression quantitative trait loci influence DNA damage-induced apoptosis in cancer

  The analysis of e2QTL allows for the identification of context-specific eQTL effects (Kim-Hellmuth et al. (2017), PMID: 28814792). To evaluate how inter-individual genetic variability influences the regulation of DNA damage-induced apoptosis, we performed e2QTL analysis of CD8+ T cells from 461 healthy European participants stimulated with high doses of 5 different carcinogens. These include Methyl-methanesulfonate (MMS), tert-butyl-hydroperoxide (TBOOH), benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE), 4-hydroxycyclophosphamide (HC) and UVC radiation.

  Study EGAS50000000666

• 2017_ AML WGS analysis result

  This data is belong to 2017 AML genome data which is aligned to human reference(human_g1k_v37.fasta). There are 10 paired tumor/normal samples from SNUH. All samples has passed QC and recalibration steps while aligning to reference.

  Dataset EGAD00001003599

• 2017_ AML prospective data analysis result

  This data is belong to 2017 AML prospective data which is aligned to human reference(human_g1k_v37.fasta). There are 10 paired tumor/normal samples from SNUH. All samples has passed QC and recalibration steps while aligning to reference.

  Dataset EGAD00001003598

• methylation_risk_reducing_surgery_breast

  Raw methylation data from breast tissue collected during risk-reducing surgery in BRCA1/2 mutation carriers.

  Dataset EGAD00010002075

• sn-RNAseq profiling of the impact of a cytokine storm model in human cardiac organoids

  We developed conditions to model conditions of diastolic dysfunction caused by inflammatory factors in human cardiac organoids. Our organoid model is based on conditions promoting maturation (Mills et al., PNAS, 2017 and Voges et al., In Revision) and incorporating human pluripotent stem cell derived cardiomyocytes, epicardial cells, fibroblasts, endothelial cells and pericytes. Following 15 days of differentiation (Voges et al., Development, 2017) we formed human cardiac organoids incorporating both our multicellular differentiation (Mills et al., PNAS, 2017) and additional endothelial cells (Voges et al., In Revision). After another 12 days of maturation in 5 days maturation medium and 5 days weaning medium (Voges et al., In Revision) human cardiac organoids were either treated with weaning medium or “cardiac cytokine storm” comprised of 100 ng/ml IFNg, 10 ng/ml IL-1 β and 10 µg/ml poly(I:C). After 48 hours human cardiac organoids were harvested and snap frozen in -80C before nuclei isolation and single nuclei RNA sequencing.Pooled hCO (~40) were homogenized in 4 mL lysis buffer (300 mM sucrose, 10 mM Tris-HCl (pH = 8), 5 mM CaCl2, 5 mM magnesium acetate, 2 mM EDTA, 0.5 mM EGTA, 1 mM DTT)(all Sigma-Aldrich) with 30 strokes of a dounce tissue grinder (Wheaton). Large pieces of hCO were allowed to settle and homogenate was passed through pre-wetted 40 µm cell strainers (Becton Dickinson). Remaining hCO material in the douncer was resuspended in 4 mL and the douncing and filtering steps were repeated twice. All steps of the homogenization were performed on ice. The filtered homogenate was centrifuged at 1500 x g for 5 min at 4oC. Nuclei pellets were then re-suspended in PBS. A fraction of resuspended nuclei were then stained with hoechst nuclear stain (1:500 dilution) and counted on a haemocytometer under fluorescent microscope.The nuclei were then re-centrifuged (1500 x g for 5 min at 4°C) and resuspended at a density to load ~5,000 nuclei per sample. Cell were loaded into the Chromium Controller (10X Genomics) for gel bead emulsion (GEM) formation. Library preparation was conducted according to the manufacturer’s recommended protocol using the Chromium Next GEM Single Cell 3’ GEM, Library & Gel Bead Kit v3.1. Libraries were sequenced on the NextSeq 500/550 v2 (Illumina) with 150 bp reads.In the snRNA-seq we note the lower than expected percentage of non-myocytes and the loss of endothelial cells (Mills et al., PNAS, 2017 and Voges et al., In Revision), indicating the protocol requires further optimization for hCO samples.

  Study EGAS00001005174

• Genetic variability in exon 1 of the glucocorticoid receptor gene NR3C1 is associated with postoperative complications

  Patients having major surgery experience inflammation post-operatively, which may contribute to post-operative morbidity. Endogenous glucocorticoids (GCs) are an essential part of the stress response, but this response varies between individuals, which may in turn affect clinical outcome in general, and post-operative inflammation, specifically. Exon 1 of the NR3C1 gene, encoding the glucocorticoid receptor, contains an established region of differential regulation. DNA methylation patterns in this region have been found to differ between individuals. We investigated the methylation status and genotype in the Cytosine-phosphate-Guanine (CpG) island in exon 1 of NR3C1 in 24 patients who underwent major abdominal surgery and correlated it with post-operative complications. DNA was extracted from peripheral blood leukocytes and underwent targeted bisulfite sequencing of the CpG island. Complications were graded according to the Clavien-Dindo classification and 14 out of 24 had post-operative complications. Multifactorial and partial least square methods were used to analyse the data. A homogenous demethylated pattern was observed in all patients and no single CpG methylation was associated with post-operative complications. Four single nucleotide polymorphisms (SNPs) were significantly correlated with higher Clavien-Dindo scores. Genetic variability in the chr5:143,402,505-143,405,805 region of exon 1 of the glucocorticoid receptor gene NR3C1, but not DNA methylation, was associated with more severe post-operative complications in patients having major abdominal surgery. This indicates that the response to GCs may be of clinical importance for inflammatory conditions.

  Study EGAS00001005737

• UCL Translation Uro-Oncology Data Access Committee will govern access to data generated from the Translation Uro-Oncology groups of the UCL Cancer Institute and UCL Division of Surgery & Interventional Science

  Dac EGAC00001000471

• Enrichment Data

  Fresh fecal samples were donated from healthy individuals. We evaluated the responses of healthy adult fecal microbiota to distinct carbon source conditions, pH levels and redox potentials. Metabolite concentrations were measured by HPLC. The total genomic DNA was extracted, sequenced and analyzed. The research project was approved by the Ethic Committee of the Canton of Zurich (2017-01290).

  Dac EGAC50000000346

• Left Atrial Cardiomyocyte Transcriptomic Analysis of Postoperative Atrial Fibrillation

  After IRB approval and informed consent, cardiomyocytes were isolated from human left atrial tissue samples obtained along the standard atriotomy incision during mitral valve surgery. RNA was isolated from cardiomyocytes and RNA libraries were prepared after rRNA depletion. RNA sequencing and whole transcriptome analysis were performed to identify differential gene expression associated with new onset postoperative atrial fibrillation.

  Study phs003644

• A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer (D-Beyond)

  This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.

  Dataset EGAD00001004391

• White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer

  Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA alterations (ctDNA) through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative chemotherapy in patients with operable gastric cancer. After filtering alterations derived from matched white-blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.

  Study EGAS00001004114

• Single-cell analysis of upper airway cells reveals host-viral dynamics in influenza infected adults

  This observational study was designed to determine the cellular tropism of Influenza A and B Viruses (IAV, IBV) from samples taken from the upper respiratory tract collected during routine nasal washes during the 2017-2018 season. Using single-cell RNA sequencing (scRNA-seq) we sought to determine which cell types could be infected, what the cellular response was to infection in both infected and bystander cells, and to compare the intra/inter-host variability of IAV and IBV during a single season at a single healthcare provider location.

  Study phs002039

• The NIHR BioResource Rare Diseases BRIDGE consortium sequencing projects

  The NIHR BioResource Rare Diseases BRIDGE consortium is a collaboration between 13 Rare Disease projects that aim to discover the genetic sequence variants underlying unresolved inherited disorders and to improve identification of already identified high penetrance variants. BRIDGE projects cover a variety of rare disease research areas including Cardiovascular, Infection and Immunity and Neuroscience. The consortium aims to sequence 8,000 samples across the different projects by 2017.

  Study EGAS00001001012

• Autozygosity pilot - Born in Bradford (2017-05-11)

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing cohort samples from the Born In Bradford study will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples. This dataset contains all the data available for this study on 2017-05-11.

  Dataset EGAD00001003329

• The Incidence of Thromboembolic Events in Patients with Antibodies to Heparin-PF4 after Cardiac Bypass

  The purpose of this study is to determine how often heart surgery patients who receive heparin develop an immune response (heparin-induced thrombocytopenia) that leads to clots forming in different parts of the body. These clots usually occur in the legs (deep venous thrombosis or DVT) or lungs (pulmonary embolism or PE) or cause heart attacks (myocardial infarction or MI) and strokes.

  Study phs000606

• CD4 T Cell Subsets in Human Metastatic Melanoma

  We used single-cell RNA-sequencing (scRNA-seq) to define CD4+ T-cell subsets in melanoma tumors from patients undergoing tumor resection. All patients received immune checkpoint blockade prior to surgery. We identified multiple subsets in the tumor with transcriptional features of suppressive function, including TR1 cells and FOXP3+ Treg cells. Based on transcriptional profiles, classical helper T cell subsets were not prevalent.

  Study phs003816