12035 results for "1m coins fc 26 Visit Buyfc26coins.com for latest FC 26 coins news..e3gh"

in 19.37 milliseconds.

• Integrative analysis of exome-seq, RNA-seq, ATAC-seq (bulk and single-cell), and Hi-C data generated from 3-D spatially mapped samples acquired during surgical resection from 10 patients diagnosed with IDH-WT glioblastoma

  Glioblastoma (GBM), the most common primary brain cancer in adults, remains incurable with no targeted therapies approved despite decades of investigation into its molecular landscape. Treatment failure is attributed to intratumoral heterogeneity in the GBM genome and epigenome, which foster tumor evolution and selection of resistant clones. However, tumor evolution and intratumoral heterogeneity remain poorly understood on the level of the whole tumor as most studies are based on single samples per patient and lack spatial context. Here, we have used 3-D neuronavigation during surgical resection for 10 primary IDH-WT GBM patients to collect 102 samples representing maximal tumor diversity, each mapped by 3-D spatial coordinates. We have applied a strategic set of genomic and epigenomic assays spanning multiple levels of resolution to discover, orthogonally validate, and functionally assess drivers of tumor evolution and intratumoral heterogeneity. These include extrachromosomal DNA amplifications, chromothripsis events, inversions, and translocations that disrupt both the GBM genome and epigenome while generating fusion transcripts and opportunities for therapeutic intervention. We define epigenomic programs that contribute to GBM evolution and intratumoral heterogeneity, revealing their 3-D spatial patterning within whole tumors and their cell type(s) of origin in single-cell data from the same tumor samples. Notably, we distinguish neuronal, glial, and immune programs aberrantly active in tumor cells from their counterparts in normal cells and discover NEUROD1, JUN/FOS, and NF1 transcription factors as key drivers of GBM evolution and growth. Collectively, these data provide unprecedented insight into GBM evolution and intratumoral heterogeneity from single-cell to whole-tumor resolution, redefining current understanding and providing a rich resource of targets for therapeutic investigation.

  Study EGAS00001006785

• cfDNA dataset from the urine supernatant of ovarian cancer patients and healthy controls

  Background Ovarian cancer is the deadliest gynecological malignancy worldwide, due to frequent diagnosis at advanced stage. Simple and non-invasive methods for earlier and accurate detection are urgently needed. Here, the presence of tumor-derived DNA in home-collected urine, cervicovaginal self-samples and clinician-taken cervical scrapes of ovarian cancer patients was explored by DNA methylation and copy number analysis. Methods A total of 428 samples (urine, cervicovaginal self-samples, and clinician-taken cervical scrapes) of 110 healthy controls and 54 patients with benign (n=25) or malignant (n=29) ovarian masses were analyzed. Different urine fractions were examined (full void urine, urine supernatant, and urine sediment). All samples were tested for 12 methylation markers by quantitative methylation-specific PCR. Shallow whole-genome sequencing was performed to detect copy number aberrations and verify the presence of tumor-derived DNA. Results Full void urine was most discriminatory between healthy controls and ovarian cancer patients (C2CD4D, p=0.008; CDO1, p=0.022; MAL, p=0.008), followed by cervical scrapes (C2CD4D, p=0.001; CDO1, p=0.004). A significant difference between benign and malignant ovarian masses was only observed for GHSR in the urine sediment (p=0.024). Methylation levels in cervicovaginal self-samples did not discriminate between healthy controls, benign and malignant ovarian masses. Copy number changes were identified in 17% of urine supernatant samples and smaller fragment sizes were seen in urine supernatant samples with a high tumor fraction. Conclusions This study demonstrates the presence of ovarian cancer-derived DNA in home-collected urine. Additional studies are warranted to further explore the clinical applicability of this approach.

  Study EGAS00001007238

• Whole genome sequencing of tumor samples from advanced pre-treated NSCLC patients recruited in a phase I/II single-arm trial utilising CVA21, an oncolytic coxsackie virus, in combination with pembrolizumab.

  Acquired or de novo resistance to immune checkpoint inhibitors occurs in the majority of advanced non-small cell lung cancers (NSCLC). There is an unmet need to improve outcomes for patients with this condition. Oncolytic viruses represent an attractive treatment approach due to their dual activity in inducing tumor cell lysis directly and potentially augmenting anti-tumor immunity. Here, we present the safety, efficacy and translational findings from a phase I/II single-arm trial utilising CVA21, an oncolytic coxsackie virus, in combination with pembrolizumab in patients with advanced pre-treated NSCLC. We performed paired biopsies pre- and post-treatment in 10 patients who received intravenous CVA21 and pembrolizumab, 8 of whom had prior treatment with immune checkpoint inhibitor (ICI) therapy. Whole genome sequencing and spatial proteomics were performed to comprehensively characterise the response to CVA21. Combination CVA21/pembrolizumab (anti PD-1) therapy was well tolerated with no serious treatment-related adverse events. Partial responses were seen in two patients with prior acquired anti-PD-1 resistance and disease stabilisation in 6 patients, giving a clinical benefit rate of 80%. High baseline tumor mutational burden and PD-L1 expression were observed in patients with better response to treatment. Interestingly, an increase in antigen presentation and CD8+ T cell infiltration was observed on treatment compared with baseline in patients with better progression-free survival. This study demonstrates the potential of CVA21 to modulate the immunogenicity of tumor cells and remodelling the tumor microenvironment, providing novel insights for patient selection for trials involving novel immunotherapeutic approaches.

  Study EGAS00001008258

• Center for Common Disease Genomics [CCDG] - Cardiovascular: Genetics of Coronary Heart Disease - Characterizaton of Coronary Prone Pedigrees

  The primary cohort includes samples from 499 men and 154 women who survived a myocardial infarction, percutaneous transluminal angioplasty, or coronary artery bypass grafting (CABG) by age 55 years for men or age 65 years for women. Patients were seen at least six months after their acute event. Samples from another 488 men and 541 women that showed a nearly identical age, gender, and measured blood pressure distribution were collected as population-based controls. These controls tended to live in urban Salt Lake City, where the vast majority of the population is Caucasian. Blood samples were collected in the morning after 12h to 16h of fasting and prepared according to guidelines of the Lipid Research Clinic's program Manual of Laboratory Operations. All samples have serum, DNA and/or white blood cells, and a host of measurements (e.g. standard clinical chemistries, LDL and HDL cholesterol, triglycerides, glucose, HbA1C, insulin, blood pressures, anthropometric data, information on medical conditions and drug use, etc.). Additional details about the cohort or sample preparation were published previously. Here we present in total 1,475 patients that were successfully sequenced. This number includes 228 women, 419 men, and 7 of unreported gender survivors as well as 339 women and 482 men that served as population-based controls.

  Study phs001901

• Transcriptome sequencing of gingivo-buccal oral squamous cell carcinoma for integrative analysis: alterations in expression of genes attributable to methylation changes

  Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the most common cancer among men in India and is associated with high mortality. Although OSCC-GB is known to be quite different from tongue cancer in its genomic presentation and its clinical behavior, it is treated identically as tongue cancer. Predictive markers of prognosis and therapy that are specific to OSCC-GB are, therefore, required. To achieve this, we have carried out transcriptome (n=72) profiling of paired tumor-normal tissues collected from OSCC-GB patients from India. RNA sequencing was performed on tumor and paired adjacent normal samples from 72 OSCC-GB patients. From each patient, total RNA was extracted from tumor and normal tissue samples using AllPrep DNA/RNA Mini Kit (QIAGEN). The quality and concentration of isolated total RNA were checked using Agilent 2100 Bioanalyzer and NanoDrop 2000 (Thermo Fisher Scientific). The OD260/OD280 ratio was ≥ 2 and RNA Integrity Number (RIN) was ≥ 7.0 for all sequenced samples. Ribosomal RNA (rRNA) was removed from the RNA samples, using Ribo-Zero Magnetic Kit (Epicentre). Sequencing libraries were prepared from rRNA depleted samples using TrueSeq RNA Sample Preparation Kit (Illumina). Each triplex cDNA library pool was sequenced as 100bp paired-end on HiSeq-2000 or HiSeq-2500 (Illumina). Protocols suggested by the manufacturers were used for all assays.

  Study EGAS00001003893

• Patient-derived tumor organoids for personalized medicine in a rare case of hepatocellular carcinoma with neuroendocrine differentiation.

  We report the case of a 74-year-old man with a very rare subtype of hepatocellular carcinoma with neuroendocrine differentiation (HCC-NED). The patient presented with two independent tumors, a gastrointestinal stromal tumor in the stomach and a hepatocellular carcinoma in the liver. Both tumors were surgically removed in curative intent. Histopathological work-up of the liver tumor revealed poorly differentiated hepatocellular carcinoma (Edmondson-Steiner grade IV) with diffuse expression of neuroendocrine markers synaptophysin (SYP) and chromogranin (CHGA). Three months after resection, multifocal recurrence of the HCC with neuroendocrine differentiation (HCC-NED) was observed. In the meantime, tumor organoids have been generated from the resected HCC-NED and extensively characterized. Sensitivity to a number of drugs approved for the treatment of HCC or neuroendocrine carcinomas was tested in vitro. Based on their in vitro efficacy, etoposide and carboplatin were used as first line palliative combination treatment. Because genomic analysis revealed a NTRK1-mutation (kinase domain) and tumor organoids were sensitive to entrectinib, a pan-TRK inhibitor, the patient received entrectinib as second line therapy. After only two weeks, treatment had to be discontinued due to deterioration of the patient’s general condition. In conclusion, we demonstrate for the first time that preclinical drug testing using organoids is feasible in selected HCC cases.

  Study EGAS00001005887

• Machine Learning Signal Enrichment for Ultrasensitive Plasma Tumor Burden Monitoring

  In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by 300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables de novo mutation calling in melanoma and small cell lung cancer (SCLC) without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).

  Study EGAS00001007451

• Machine learning guided signal enrichment for ultrasensitive plasma tumor burden monitoring

  In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by 300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables de novo mutation calling in melanoma and small cell lung cancer (SCLC) without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).

  Study EGAS00001007545

• Genetic_variation_in_Kuusamo

  The aim of this study is to characterize as completely as possible the genetic variation and structure of Kuusamo and surrounding regions. We will perform low coverage, whole genome sequencing in a relatively limited number (approximately 200) of individuals from the FINRISK study both of whose parents are born in Kuusamo, Posio or Taivalkoski. Sequencing will be performed at the Wellcome Trust Sanger Institute (WTSI). We have previously shown using simulations and genome wide SNP data that the genetic characteristics agree with known genealogical data, and that approximately 200 individuals suffice to capture the majority of the genetic variation in this population.We have also developed methods for long-range haplotyping and long-range imputation, which are more accurate than traditional methods. This will allow us to identify a majority of the founder haplotypes in this population. The information from the haplotypes identified in this study can be used in other studies to impute from genome-wide SNP data the full genome sequence of samples ascertained for specific phenotypes.

  Study EGAS00001000020

• Offspring Sex Impacts DNA Methylation and Gene Expression in Placentae from Women with Diabetes during Pregnancy

  Exposure to diabetes in utero is known to increase the offspring's likelihood of developing metabolic disease in adulthood, but the mechanisms involved are unknown. It has been proposed that early exposure to hyperglycemia and elevated insulin levels may lead to malprogramming of the fetus leading to the subsequent development of diabetes and obesity. Epigenetic modifications of the genome including DNA methylation, provide a plausible mechanism that allows for permanent propagation of gene activity states from one generation of cells to the next. The placenta, a fetal tissue easily accessible for study, is a complex organ that is essential in regulating fetal growth. The changes in placental nutrient transport associated with diabetes during pregnancy (DDP) have significant effects on the developing fetus, indicating that the placenta plays a critical role in fetal programming. The aim of our study was to investigate whether exposure to DDP alters genome-wide DNA methylation in the placenta obtained from term pregnancies resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression.

  Study phs001535