10919 results for "division 1 coins fc 26 Buyfc26coins.com is FC 26 coins official site..AwVj"

in 13.96 milliseconds.

• Conserved features of TERT promoter duplications reveal an activation mechanism that mimics hotspot mutations in cancer

  Mutations in the TERT promoter are the single most common non-coding mutation in cancer and represent the genetic underpinnings of tumor cell immortality. Beyond the two most common point mutations, G228A and G250A, which selectively recruit the ETS factor GABP to activate TERT, the significance of other variants in the TERT promoter are unknown. We identified duplications of wildtype sequence within the core promoter region of TERT in 7 different cancer types that have strikingly similar features including size, insertion position, and inclusion of one of the native ETS motifs. Each duplication activates the TERT promoter to a similar level as G228A and G250A and is critically dependent on the insertion site. The GABP tetramer binds to the TERT duplicated promoter sequence by virtue of the native ETS motif and its duplicated version with precise spacing, and it is necessary for the transcriptional activation by all duplications tested. Spatiotemporal analysis in a multifocal glioblastoma shows the duplication is clonal and its activation of TERT is readily detectable at the single cell level and in bulk tumor tissue. We conclude that recurrent TERT promoter duplications of the native ETS sequence are functionally and mechanistically equivalent to the hotspot mutations that confer tumor cell immortality. The shared mechanism of these divergent somatic genetic alterations suggests a strong selective pressure for recruitment of the GABP tetramer to activate TERT.

  Study EGAS00001006118

• Whole exome sequencing of SU- DIPG-XIII from different sites

  Whole exome sequencing of diffuse intrinsic pontine glioma (DIPG) cells isolated from the pons and from a sub-ventricular zone site of spread within the frontal lobe from the same individual (SU- DIPG-XIII)

  Dataset EGAD00001003563

• DNA demethylation is associated with malignant progression of low-grade gliomas

  To elucidate the mechanisms of tumor progression is key to discovering strategies for treating patients with lower-grade glioma. Thus to characterize the changes in the molecular profile during malignant progression, we performed methylation array analysis (122 tumors), whole-exome sequencing (36 tumors and matched normal samples), and RNA sequencing (31 tumors). This cohort included 24 matched pairs of initial lower-grade gliomas and recurrent tumors, most of which showed malignant progression when they recurred. Nearly half of IDH-mutant glioblastomas that had progressed from lower-grade gliomas exhibited characteristic partial DNA demethylation in previously methylated genomic regions of their corresponding initial tumors, which had the glioma CpG island methylator phenotype (G-CIMP). In these glioblastomas, cell cycle-related genes were upregulated, RB and PI3K-AKT pathway genes were frequently altered. Notably, bioinformatics analysis revealed that late-replicating domain was significantly enriched in the demethylated regions that were mostly located in non-regulatory regions, suggesting that the loss of DNA methylation during malignant transformation may involve mainly passive demethylation due to a delay in maintenance of methylation during accelerated cell division. Nonetheless, a limited number of genes including IGF2BP3, which potentially drives cell proliferation, were presumed to be upregulated due to demethylation of their promoter. Thus, cell proliferation was further promoted by passive demethylation in the promoter region of these oncogenic genes. Our data indicated that demethylation of the G-CIMP profile found in a subset of recurrent gliomas reflects accelerated cell divisions accompanied by malignant transformation. Oncogenic genes activated by such epigenetic change represent potential therapeutic targets.

  Study JGAS000146

• Study of Women's Health Across the Nation (SWAN) Repository

  The Study of Womens Health Across the Nation (SWAN) is an active multi-site, multi-disciplinary, longitudinal study of women's health. Initially funded in 1994 by the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the Office of Research on Women's Health (ORWH), the overall goal of SWAN is to describe the natural history of the menopausal transition and the post menopause including biological, behavioral, and psychosocial characteristics. SWAN focuses on the impact of menopause on age-related chronic diseases, such as diabetes, cardiovascular disease, depression, bone loss and osteoporosis, as well as physical and cognitive functioning. SWAN has seven clinical study sites located in six states, two in California, and one each in Chicago, Boston, Detroit area, northern New Jersey and Pittsburgh. The SWAN cohort was recruited from these areas and consists of 3,302 African American, Caucasian, Chinese American, Hispanic and Japanese American women. SWAN participants were enrolled in 1996-1997 and have been seen annually or bi-annually for clinic visits, which include interviews, measurements, and the collection of blood and urine samples. SWAN participants have now been seen for the baseline and 15 follow-up visits.

  Study phs001470

• Integrated Genomic Analysis of Periampullary Tumors at The Human Genome Sequencing Center, Baylor College of Medicine (HGSC-BCM)

  Adenocarcinomas arising in the complex environment of the ampulla of Vater constitute a histopathological heterogenous group, presumably originating from the different epithelial cellular constituents present at the site: pancreas, bile duct, and intestinal duodenum. These tumors have been described in many different ways: intra-ampullary, periampullary, intra-ampullary papillary-tubular neoplasm, ampullary-ductal, periampullary-duodenal, and ampullary-not otherwise specified. These varied classifications reflect the difficulty in classifying these tumors into specific groups. Only the tumors clearly localized in the bile duct or duodenum are identified as distal cholangiocarcinomas (CAC) or duodenal adenocarcinomas (DUOAC). The current classification is based on macroscopic features that may distinguish the epithelium of origin, microscopic features, clinicopathological criteria, histopathology and expression of differential markers. This classification is subjective and prone to inter-observer variability and significantly impacts on treatment selection and therapeutic development. In order to define subtypes of periampullary cancer with clinical relevance, we performed whole exome sequencing and copy number analysis of 160 cancers arising in the periampullary region, 62 of these clearly arising from either the bile duct (n = 44), or the duodenum (n = 18) and 98 periampullary cancers (AMPAC) where the epithelium of origin could not be clearly defined.

  Study phs000895

• Mutational Patterns in Metastatic Cutaneous Squamous Cell Carcinoma

  Cutaneous squamous cell carcinoma (cSCC) from the head and neck typically metastasizes to the lymph nodes of the neck and parotid glands. When a primary is not identified, they are difficult to distinguish from metastases of mucosal origin and primary salivary gland SCC. Ultraviolet radiation causes a mutation pattern that predominantly features cytosine to thymine transitions at dipyrimidine sites and has been associated with cSCC. In this study, we used whole genome sequencing data from 15 cSCC metastases and show that a UV signature mutation is pervasive across the cohort and distinct from mucosal SCC. The mutational burden was exceptionally high and concentrated in some regions of the genome, especially insulator elements (mean 162 mutations / Mb). We therefore evaluated the likely impact of UV-induced mutations on the dipyrimidine rich binding site of the main human insulator protein, CCCTC-binding factor (CTCF), and the possible implications on CTCF function and the spatial organization of the genome. Our findings suggest that mutation signature analysis may be useful in determining the origin of metastases in the neck and the parotid gland. Furthermore, UV-induced DNA damage to insulator binding sites may play a role in the carcinogenesis and progression of cSCC.

  Study EGAS00001003370

• META-PRISM

  A pan-cancer cohort of 1031 patients resistant to systemic therapies or with no approved therapeutic options. It includes whole-exome sequencing of 571 tumor and matched-normal samples, and transcriptome sequencing of 947 tumor samples. Biopsies were taken at entry into precision medicine trials, often after diagnosed resistance. Comprehensive clinical information is available for all patients and include patient age at biospy, tumor primary site and histological subtype, biopsy site, treatments received prior to biopsy, blood assessment results at biopsy, metastatic sites at biopsy, and survival time from the biopsy date.

  Dataset EGAD00001009684

• FEGA and European GDI: working together to improve human health

  The Federated EGA is a global resource for discovery of and access to sensitive human omics and associated data consented for secondary use, through a network of human data repositories to accelerate biomedical research and improve human health. The Federated EGA network was launched in September 2022 with five inaugural nodes, and since 2023 seven operational nodes can share data across national borders in adherence to European and national laws. A few weeks after FEGA's official launch, in November 2022, the European Genomic Data Infrastructure (GDI) project was kicked-off . This European Commission co-funded project, coordinated by ELIXIR, is aimed to deliver federated, sustainable and secure data infrastructure to access genomic and related phenotypic and clinical data across Europe. This project supports the aim of the 1+MG initiative (25 EU countries, Norway and UK) to enable personalised medicine and health through a shared framework and infrastructure for securely accessing and integrating high quality genomic data and other health data across borders.1+MG will be an integral component of the European Health Data Space (EHDS) for secondary use (Healthdata@EU) as an authorised participant. How are Federated EGA and GDI similar? Given their shared visions, the Federated EGA and European GDI networks have a lot in common. To begin, they share the same overall goal of establishing networks of “nodes” that host sensitive human data within a jurisdiction and connecting these nodes in a global network to support data discovery and promote human genome data access for research and healthcare. FEGA and GDI are both initially focused on enabling access to human genomic data, while FEGA ambition is to expand the scope to clinical research data and other omics data in the future. FEGA and GDI are both built on open and interoperable software solutions, a subset of which are based on the LocalEGA components. FEGA and GDI implementation solutions are based on international community standards, for example those developed by the Global Alliance for Genomics and Health, which contributes to making them interoperable. Both FEGA and GDI allow for the nodes to make use of any solution that is fully compatible. As illustrated in Figure 1, a final key point is the significant overlap of institutions involved in envisioning and operating FEGA and GDI nodes, with the clear wish to keep them interoperable in the future. What distinguishes Federated EGA from GDI? Despite being largely similar, there are some differences between the FEGA and GDI networks, which we aim to clarify in this post. The first difference is the governance model that the nodes will operate to comply with national laws and GDPR. In the FEGA network, nodes have taken inspiration from the EGA data access model, where the infrastructure is a data processor of the hosted data and data controllership remains with the originating Data Access Committees (i.e. Data controllers) for each dataset. On the other hand, in the GDI network the controllership of datasets will be transferred to a 1+MG European Digital Infrastructure Consortium (EDIC) legal entity created by the Member States (MS), who will make data access decisions, with data holders having veto powers for their datasets. Importantly, FEGA nodes have the flexibility to choose another model to fit with their data protection framework, including becoming data controllers for their datasets. The second difference is the inclusion criteria for data. While FEGA nodes are designed to accept almost any type of omics data in need of control access (e.g. genomics, transcriptomics, genotyping, single cells sequencing, patient-tracked metagenomics), GDI nodes are initially, but not only, focused on accepting whole genome and exome sequencing data and affiliated data from sources such as (i) the Genome of Europe use case of the 1+MG initiative which specifically aims to fulfil the mission of building “a European network of national genomic reference cohorts of at least 500,000 citizens”) (ii) data collection of other types of genomic data identified by countries through the 1+MG dashboard and (iii) genomic data coming from data holders which would need to fulfil EHDS requirements. The third difference is the maturity of the software stacks. The FEGA network provides a set of software for data and metadata submission, storage, permissions management, and file distribution (the LocalEGA package). GDI is building a complete set of open source reference for the five functionalities covering the full data life cycle (a few more compared to the LocalEGA) including federated processing (analytics, AI/ML), which is still under active development. Notably, one of the GDI functionalities - storage and interfaces - can be satisfied by using the LocalEGA storage solution, highlighting the ability of FEGA and GDI to be interoperable. In both FEGA and GDI, nodes are allowed to use alternative solutions as long as they are fully interoperable with the networks. Figure 1 provides a simple overview of these described commonalities and differences. Figure1: schematic overview of the main commonalities and difference among a FEGA and a GDI node Can the same institute run a FEGA and a GDI node at the same time? The answer is Yes! We believe this is entirely possible and encouraged. As long as 1+MG requirements are continuously fulfilled in the implementation. The same trained personnel could operate the infrastructure and leverage the same national funding to run a FEGA and a GDI node. Several European nodes, especially GDI vanguard nodes like Norway, Sweden, Finland and Spain are following this model. The idea is that a lot of the work can be reused, given the overlapping scope and the interoperable technology. Thus, the hosted datasets can be discovered via the two catalogues, perhaps accessible under the same or different governance models. From a FEGA node perspective, the GDI datasets could simply be a subset of the datasets hosted in the FEGA node, which have their specific governance as any other. What's next? So, the amazing teams of people building the Federated EGA network and the European GDI network are working together to create infrastructures able to provide secure access to human genomic and associated data around Europe. Because we all know how much human genomics can improve healthcare and precision medicine. And we all want to collaborate to make it happen. This article has been reviewed collectively by members of the EGA and the GDI coordination team.

  Blog fega-and-gdi

• A Genome-Wide Association Study in Patients Experiencing Musculoskeletal Adverse Events on NCIC CTG Trial MA.27 Evaluating Aromatase Inhibitors as Adjuvant Therapy in Early Breast Cancer. A Collaboration Between the NIH Pharmacogenetics Research Network and the RIKEN Yokohama Institute Center for Genomic Medicine.

  Source of Patients The source of the patients for this genome-wide case control study was MA.27, which was conducted as a multi-cooperative group effort under the auspices of the NCI Breast Cancer Intergroup of North America. The NCIC Clinical Trials Group (CTG) serves as the coordinating group, with participation by the NCI-sponsored North Central Cancer Treatment Group, Eastern Cooperative Oncology Group (ECOG), Southwest Oncology Group, and Cancer and Leukemia Group B (CALGB). MA.27 involved postmenopausal women with histologically confirmed and completely resected invasive breast cancer with surgical margins clear of invasive carcinoma and DCIS in the following TMN categories (AJCC Version 6): pT1, pT2, pT3; pNx, pN0, pN1, pN2, pN3 (only when the sole basis is presence of 10 or more involved axillary nodes); MO. The primary tumor must have been ER and/or progesterone receptor positive. Patients were stratified by lymph node status at diagnosis, prior adjuvant chemotherapy, and trastuzumab use and were randomized to 5 years of adjuvant therapy with anastrozole or exemestane. The trial was activated on May 26, 2003, and reached its accrual objectives on July 31, 2008, after the randomization of 6827 North American patients, with the majority (79%) providing DNA and consent for genetic testing. Non-North American patients were also entered by the International Breast Cancer Study Group but they did not contribute DNA. From 2003 to December 21, 2004, patients also underwent a second randomization to celecoxib 400 mg twice daily or placebo but, after the entry of 1,622 patients, this treatment was discontinued because of reports of increased cardiovascular risk associated with celecoxib. Case Definition for Musculoskeletal Adverse Events Cases were defined to have had at least one of the following six MSAE): 1. pain - joint, 2. pain - muscle, 3. pain - bone, 4. arthritis, 5. joint - function, 6. musculoskeletal - other. Cases were required to have at least grade 3 toxicity, according to the NCI Common Terminology Criteria for Adverse Events v3.0, or go off treatment for any grade of the six MSAEs; and were required to have had an MSAE within the first two years (i.e., a MSAE occurring after 2 years was not be considered a case). Subjects were excluded from the case group who met the case definition while on celecoxib or in the three months after stopping celecoxib but subjects were allowed to be cases if they developed their first MSAE more than three months after stopping celecoxib. Study Design The design was a nested matched case-control study with two controls selected for each case. Random matching from the potential control group (i.e., risk-set sampling such that controls had at least the same length of followup as the timing of the case event) was done by matching the case on the following factors: 1. treatment arm (exemestane vs. anastrozole, blinded), 2. prior adjuvant chemotherapy (yes vs. no), 3. age at start of treatment (+/- 5 years), 4. Celecoxib allocation (yes vs. no). Attempts were made to exactly match each case with two controls according to the above criteria. If, however, controls could not be exactly matched, "close" matching was used to define a distance between each case and all potential controls in an optimal matching algorithm. Race is a potential confounding factor, and 94% of the MA.27 population is Caucasian, 3% are Black, 1% Asian, 1% American Indian, and 1% are of unknown race. Because there are so few non-Caucasian participants, was restricted to only Caucasians. Following identification of cases and controls, the list was sent to the CALGB Pathology Coordinating Office (PCO) at Ohio State University Medical Center for plating of the samples. Other patient factors that might influence the association of SNP genotypes with a MSAE, either as confounding factors or as effect modifiers, were included as investigational covariates. These include 1. body mass index (BMI), 2. bisphosphonate use, 3. fractures in past 10 years, 4. baseline ECOG performance status, 5. prior hormone replacement therapy, 6. prior adjuvant radiotherapy, and 7. prior taxane treatment. An Honest Broker Process was utilized to ensure patient confidentiality. Genotype Assays and Quality Control A GWAS was performed with the Illumina Human610-Quad at the RIKEN Center for Genomic Medicine. The DNA for all of the samples were adjusted to a concentration of 50 to 100 ng/µL in a final volume of 50 µL. The 96-well plates were designed to have a unique distribution pattern with x duplicates per plate to evaluate genotype concordance. Samples with <98% call rate were removed from analyses. SNPs with ambiguous call will be excluded using the following criteria: 1. low signal intensity of each allele, 2. low cluster separation score, 3. SNP call rate <0.98, 4. SNPs with Hardy Weinberg Equilibrium p-value <0.001 were excluded. X-chromosome SNPs were used to validate female sex and quality control measures were examined across the different submitting centers. For all pairs of subjects, the percentage of matching genotypes were computed to screen for unexpected duplicate samples. All SNPs found to be associated with MSAE were subjected to visual inspection of the cluster plots to verify that the genotype clustering was adequate.

  Study phs000210

• Childhood Cancer Data Initiative (CCDI): Pediatric In Vivo Testing Program – Sarcomas and other Solid Tumors

  The primary goal of this project involves the comprehensive molecular profiling of patient-derived xenograft (PDX) mouse tumor models. Molecular profiling of each PDX model will include whole exome sequencing (WES), RNAseq, MethylEPIC arrays, CytoSNP array, and DNA fingerprint for quality control. Limited clinical demographic data (e.g. diagnosis, disease site, disease status) will be obtained. This data can be utilized to validate PDX models with matched patient tumors and can be used to guide model selection for downstream preclinical drug testing.

  Study phs003161