20313 results for "Fc coins Buyfc26coins.com is EA Sports official for FC 26 coins They are efficient and quick always..Z2Xg"

in 22.56 milliseconds.

• Single-cell analysis reveals different age-related somatic mutation profiles between stem and differentiated cells in human liver

  Highly metabolic liver is exposed to many sources of spontaneous mutagenesis resulting in increased genome instability that, potentially, causes age-related functional liver failure. Here we comparatively characterize the somatic mutational landscape in single human liver cells from individuals of various ages. Mutation frequency is very high in normal human hepatocytes, increasing dramatically with age as compared to other tissues and cell types, e.g., B-cells, neurons, and clonal surrogates of various adult stem cells. Moreover, differentiated hepatocytes tend to accumulate more mutations compared to age-matched proliferating liver stem cells (LSCs). Mutation spectra also differ dramatically between different cell types. Elevated oxidative hallmarks are observed in mouse liver and ex vivo cultured LSCs, but not during liver aging. Overall, human liver is prone to high age-dependent genome instability, compared to other tissues, and reveals functional difference between LSCs and hepatocytes.

  Study phs001956

• Pheno-Seq, linking 3D phenotypes of clonal tumor spheroids to gene expression

  3D-culture systems have advanced cancer modeling by reflecting physiological characteristics of in-vivo tissues, but our understanding of functional intratumor heterogeneity including visual phenotypes and underlying gene expression is still limited. Transcriptional heterogeneity can be dissected by single-cell RNA-sequencing, but these technologies suffer from low RNA-input and fail to directly correlate gene expression with contextual cellular phenotypes. Here we present pheno-seq for integrated high-throughput imaging and transcriptomic profiling of clonal tumor spheroids derived from 3D models of breast and colorectal cancer. Specifically, we identify characteristic expression signatures that are associated with heterogeneous invasive and proliferative behavior including a rare cell subtype. Furthermore, we identify functionally relevant transcriptional regulators missed by single-cell RNA-seq, link visual phenotypes defined by heterogenous expression to inhibitor response and infer single-cell regulatory states by deconvolution. We anticipate that directly linking molecular features with patho-phenotypes of cancer cells will improve the understanding of intratumor heterogeneity and consequently prove to be useful for translational research.

  Study EGAS00001002999

• Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT-BioLINCC)

  Accessing Data: Please refer to “Authorized Access” below regarding accessing data through the BioData Catalyst ecosystem. The data from this accession is not available for download through dbGaP.Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-pro-BNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with heart failure (HF) and reduced ejection fraction (HFrEF).Background: Heart failure is a common disorder. Standard treatment for HF includes diuretics to control fluid, and drugs called "neurohormonal antagonists" (such as beta-blockers and ACE-inhibitors) to help the heart work more efficiently. The natriuretic peptides, specifically NT-pro-BNP, are biomarkers that reflect HF severity and are significantly associated with adverse outcomes in HF. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels (“guided therapy”) with inconsistent results.Participants: A total of 894 participants were enrolled at 45 sites in the United States and Canada, with 446 randomized to the NT-pro-BNP-guided strategy treatment group and 448 randomized to the usual care treatment group.Design: GUIDE-IT was a multicenter randomized clinical trial with participants randomized to either the NT-pro-BNP-guided therapy strategy or usual care. Given the nature of the study intervention, treatment assignment was not blinded. For participants randomized to the NT-pro-BNP-guided strategy, clinicians were instructed to titrate HF therapy to target an NT-pro-BNP level After an initial visit at 2 and 6 weeks, visits occurred every 3 months throughout the remainder of the study. After therapy adjustment for HF (whether driven by NT-pro-BNP levels or clinical reasons), participants had a 2-week follow-up visit for reassessment. All participants in either group also had blinded NT-pro-BNP concentrations measured in a core laboratory at each study visit. The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Conclusions: The guided strategy intervention was stopped in July of 2016 (median follow-up of 15 months) after the study met prespecified inefficacy criteria. Compared to usual care, a strategy of NT-pro-BNP-guided therapy was not more effective in improving time-to-first HF hospitalization or cardiovascular mortality in high-risk participants with HFrEF.

  Study phs003621

• FFPE CRC sequence data and somatic variants

  We included 3 BAM files of the genome sequencing data: 2 of 3 are from tumour samples, namely 1 repaired-FFPE and 1 unrepaired FFPE; the third BAM file is from normal tissue of FFPE block. There is also a VCF file containing all somatic mutations in the dataset.

  Dataset EGAD00001007723

• Gene Expression of Small Cell Carcinoma of the Ovary-Hypercalcemic Type (SCCOHT)

  Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare and aggressive form of ovarian cancer afflicting young women at a median age of 24 years. SCCOHTs are characterized by loss of protein expression of SWI/SNF chromatin remodeling ATPases SMARCA4 and SMARCA2 through mutation and epigenetic silencing, respectively. This study aims to establish gene expression profiles of this cancer through RNA-Seq of fourteen pathologically confirmed cases of SCCOHT tumors.

  Study phs001528

• ResolveCRPS study - RNA-fragment sequencing from snap-frozen skin biopsies

  Complex Regional Pain Syndrome (CRPS) is a disabling pain disorder with unclear cutaneous molecular mechanisms. To identify gene-expression signatures linked to pain intensity and disease progression, we profiled the local transcriptome of CRPS-affected skin. 42 patients agreed to skin biopsies from the CRPS-affected area, which underwent low-input total RNA-seq. Full experimental and bioinformatics protocols are provided in the associated publication and its supplementary material.

  Study EGAS50000001061

• Genes___Health_imputed_genotype_dataset

  Genes & Health is a cohort of British Bangladeshi and British Pakistani individuals. In the Feb2020 data freeze, 28,022 individuals were genotyped on the Illumina Infinium Global Screening Array v3 chip (with the additional Multi-Disease variants). Imputation was performed using the Michigan Imputation Server with the GenomeAsia pilot reference panel, which contains 1,739 genomes and 642 from them are from South Asian groups. This dataset contains imputed SNPs with imputation accuracy >0.3 and MAF >0.1%.

  Study EGAS00001005373

• Comprehensive characterization of pre- and post-treatment samples of breast cancer reveal potential mechanisms of chemotherapy resistance

  When locally advanced breast cancer is treated with neoadjuvant chemotherapy, the recurrence risk is significantly higher if no complete pathologic response is achieved. Identification of the underlying resistance mechanisms is essential to select treatments with maximal efficacy and minimal toxicity. Here we employed gene expression profiles derived from 317 HER2-negative treatment-naïve breast cancer biopsies of patients who underwent neoadjuvant chemotherapy, deep whole exome and RNA-sequencing profiles of 22 matched pre- and post-treatment tumors, and treatment outcome data to identify biomarkers of response and resistance mechanisms. Molecular profiling of treatment-naïve breast cancer samples revealed that expression levels of proliferation, immune response and extracellular matrix (ECM) organization combined predict response to chemotherapy. Triple negative patients with high proliferation, high immune response and low ECM expression had a significantly better treatment response and survival benefit (HR 0.29, 95% CI 0.10-0.85; p=0.02), while in ER+ patients the opposite was seen (HR 4.73, 95% CI 1.51-14.8; 0=0.008). The characterization of paired pre-and post-treatment samples revealed that aberrations of known cancer genes were either only present in the pre-treatment sample (CDKN1B) or in the post-treatment sample(TP53, APC, CTNNB1). Proliferation-associated genes were frequently down-regulated in post-treatment ER+ tumors, but not in triple negative tumors. Genes involved in ECM were upregulated in the majority of post-chemotherapy samples. Genomic and transcriptomic differences between pre- and post-chemotherapy samples are common and may reveal potential mechanisms of therapy resistance. Our results show a wide range of distinct, but related mechanisms, with a prominent role for proliferation- and ECM-related genes.

  Study EGAS00001005876

• Phase II Therapeutic Trial of Mexiletine in Non-Dystrophic Myotonia (IND #77,021)

  Non-dystrophic myotonias are a group of rare muscle disorders caused by abnormalities in different muscle cell membrane proteins. Patients experience delayed muscle relaxation that causes impaired physical activity, stiffness, and pain. Mexiletine has been shown to be beneficial for symptoms of myotonia in case reports of patients with non-dystrophic myotonia, however, current management of these patients primarily depends on individual practitioners' preference. This study is a placebo-controlled, double-blind, cross-over treatment trial using mexiletine in non-dystrophic myotonias. The results, if positive, will permit the identification of mexiletine as an effective therapy for myotonia, making it a first-line therapy for patients with non-dystrophic myotonia. The specific aim of this proposal is to perform a randomized, double-blind, placebo-controlled cross-over study to assess whether mexiletine improves both quantitative and qualitative measures of myotonia in patients with non-dystrophic myotonia. Given the rarity of non-dystrophic myotonia, large randomized controlled treatment trials in these disorders have not been feasible in the past. Primary Outcome Measure: Patient-assessed symptom: stiffness as measured by an Interactive Voice Response Diary (IVR). Secondary Outcome Measures: a) patient-assessed pain, weakness, and fatigue as measured by IVR; b) clinical myotonia assessment; c) quality of life as measured by INQoL, SF36; d) a quantitative measure of grip myotonia; e) measurement of CMAP after short and long exercise; f) grading of myotonia on needle EMG.

  Study phs001311

• Admixture histories of São Tomé e Príncipe.

  Genotyping datasets used in the article "Nested admixture during and after the Trans-Atlantic Slave Trade in the island of Sao Tome" by Ciccarella M et al. 2025 The genotype data corresponds to 2,104,148 autosomal SNPs genotyped from the IlluminaOmni 2.5 Million BeadChip for 97 volunteer participants sampled on São Tomé e Príncipe, family unrelated at the 2nd degree based on population genetics analyses. In particular, the dataset is composed of 95 individual samples collected on São Tomé and 2 collected on Príncipe. SNP rsID, Chromosome position and genetic position in (bp) are in Build GRCh38.

  Dataset EGAD50000001348

• Disease Variant Landscape of a Large Multiethnic Population of Moyamoya Patients by Exome Sequencing

  We report a significant advance in Moyamoya disease (MMD) research through our unique access to a large MMD patient population combined with high depth exome sequencing and bioinformatics. We confirm a reported RNF213 founder mutation (FM), provide evidence for its ethnic specificity and identify novel variants in other genes that associate with Caucasian and non-RNF213 FM MMD. This work has a broader impact in vascular research by highlighting novel genetic aspects of cerebrovascular disease. Moyamoya Disease (MMD) is a rare cerebrovascular disorder characterized by unilateral or bilateral progressive stenosis or occlusion of the internal carotid artery, with frequent involvement of the anterior cerebral artery and the middle cerebral artery (MCA). Fragile collateral vessels subsequently develop and are particularly prone to hemorrhage. MMD patients are usually diagnosed angiographically following presentation of developmental delays, seizures, migraines, ischemia, and/or hemorrhage. The most common approach to re-establish normal blood flow is bypass surgery. While some progress has been made in identifying disease-associated genes, the underlying disease biology is not well understood. Moyamoya disease (MMD) is a rare cerebrovascular disease. Our unique access to a large MMD patient population combined with high depth exome sequencing and bioinformatics has led to a significant advance in the field. We confirm a reported RNF213 founder mutation (FM), provide evidence for its ethnic specificity and identify novel variants in other genes that associate with Caucasian and non-RNF213 FM MMD. This work has a broader impact in vascular research by highlighting novel genetic aspects of cerebrovascular disease. The 125 ethnically diverse, unrelated MMD patients were matched based on sex and broad ethnic category to 125 controls. Control DNA from the 1000 Genomes project was used to design a control Library by Personalis. 125 controls were selected from this Personalis Control DNA Library for our study. (The 1000 Genomes Project Consortium 2012). Genomic DNA was extracted using the Gentra Puregene kit (Qiagen, Valencia, CA). Libraries were prepared from approximately 3 µg of high quality genomic DNA (50-200 ng/µl) using Illumina TruSeq Genomic DNA High throughput Sample Prep Kits (Illumina, San Diego, CA) and exome enrichment (targeting 62Mb) was accomplished using the TruSeq Exome Target Enrichment kit (Illumina, San Diego, CA), all according to manufacturer's protocols. Target enrichment validation was confirmed by determining the concentration of the library by PicoGreen-based quantitation. Library yields ranged from 100-1000ng of DNA, a portion of which was run on the Bioanalyzer HS DNA chip (Agilent, Santa Clara, CA), with an average size of 300-550nt for DNA fragments. Exome Sequencing. Sequencing was performed using Illumina Hiseq2000 or HiSeq2500 sequencers with single lane, paired-end 2X100bp reads. DNA fragments were generated and amplified using Clonal Single Molecule Array technology (Illumina, San Diego, CA). The sequences were determined using the Clonal Single Molecule Array and Sequencing-by-Synthesis using Illumina's instrumentation and Reversible Terminator Chemistry. Each sequencing lane interrogated the DNA sequences of a pool of 3 individual sample libraries each carrying a unique index. Sequencing reads of at least 2x100bp in length for a total of approximately 8 Gb of sequence data were generated for each sample.

  Study phs001700

• Determination_of_cell_specific_regulatory_enhancers_in_hematopoetic_models

  The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The human variation workpackage (WP10) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise “experimental noise” and therefore enhance the power to discover modest effects. Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose. The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively. Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers. This data set contains functional genomics data for gene expression and chromatin state.

  Study EGAS00001000586

• sWGS on cfDNA and matching tumor DNA in pediatric cancer

  This dataset contains shallow whole genome sequencing data from paired cfDNA - tumor DNA samples of various pediatric cancer entities. Files are provided in fastq format. Samples were sequenced on an Ion Proton sequencer (Thermo Fisher Scientific) or a Hiseq3000 (Illumina). Data analysis is available at https://github.com/rmvpaeme/sWGS_pediatric_cancer.

  Study EGAS00001005198

• Genome-wide mutation analysis of germinal-center B-cell derived lymphomas within the ICGC MMML-Seq Consortium

  Germinal-center B-cell derived lymphomas (GCB-lymphomas) are the most common B-cell lymphomas in children and adults, with Burkitt Lymphomas (BL) predominating in childhood and follicular lymphoma (FL) and diffuse large B-cell lymphomas (DLBCL) predominating in older age groups. The cell-of-origin in all these lymphomas is supposed to be a germinal center B-cell and transformation of FL in DLBCL or intermediate DLBCL/BL (intL) can occur. In the framework of the German ICGC MMML-Seq we are currently exploring sequencing data of GCB-lymphomas and paired normal controls as well as normal B-cell subsets separated by FACS. This includes whole genome, transcriptome, miRNAome and whole methylome datasets.

  Study EGAS00001000394

• A Phase 2 Study of Tipifarnib in Large Granular Lymphocyte (LGL) Leukemia

  LGL leukemia can be divided into three subsets including the following: αβ or γδT-LGL and NK-LGL leukemia. All three subtypes will be enrolled using a two-stage design. The primary endpoint of the study is assessment of overall clinical response. Correlative laboratory studies will be performed aimed at determining the mechanism of response to treatment. Thirteen participants will be accrued in the first stage at a dose of 300 mg BID administered intermittently every other week (i.e., 7 days on and 7 days off). If there are two or more responders, the protocol will be extended to a second stage of the study and accrual will be extended to 25 evaluable participants. Allowing for 10% rate of ineligibility due to unexpected events and dropout, we will accrue 14 patients in the first stage and 27 patients in total. Participants that withdraw from the study for reason unrelated to toxicity, will be replaced. There are two potential stopping rules for toxicity. If 3 or more participants out of the 13 enrolled in the first stage experiences grade IV neurotoxicity, the study will be stopped due to excessive toxicity. Dose reductions have been incorporated for hematologic toxicity. Treatment of T and NK LGL leukemia with immunosuppressive agents such as low-dose methotrexate generally require from four to six months for a clinical response and sometimes much longer. Therefore, in participants who show clinical improvement with less than grade three toxicity, tipifarnib treatment will be continued for as many as four additional months (12 months total). After the first 8 months, response will be assessed. The protocol treatment will be discontinued in participants with progression of disease. A long-term follow up will be performed for five years in patients that receive a complete clinical response. The long-term follow up will consist of vital signs, weight, CBCs, serum chemistries, and physical examination at six month intervals.

  Study phs000594

• Genome Sequencing of Pancreatic Ductal Adenocarcinoma at The Human Genome Sequencing Center of Baylor College of Medicine (HGSC-BCM)

  Pancreatic ductal adenocarcinomas (PDAC) is the 11th most common cancer in the USA but the 4th in fatalities. The onset and progression of cancer is driven by extensive rearrangement and mutation of the genome. We combined our capability to capture and enrich exome DNA with the next generation sequencing capacity to allow us to detect and characterize the somatic mutation profile of 24 patients with PDAC. Patient samples were collected by the Elkins Pancreatic Center in the Baylor College of Medicine Department of Surgery. Sequencing of the pancreatic ductal adenocarcinoma is one of the NHGRI Center Initiated Projects in progress in the Human Genome Sequencing Center at Baylor College of Medicine. These data are also contributed to an ICGC study and will be published with the ICGC collaborators.

  Study phs000516

• Genomic_profiling_of_B_other_Adult_ALL_WGS

  Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes. Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL and to date there have been no studies investigating the genomics of Adult ALL. We will perform whole genome sequencing on at least 100 Adult ALL cases. Priority will be given on ALL cases without a known primary lesion by cytogenetic analysis which are categorised as “B-other”. We will also sequence representative cases of each known subtype. This will deliver a comprehensive annotation of the genomic landscape of Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles. The focus on B-other Adult ALL is likely to result in new and previously undescribed genomic lesions.

  Study EGAS00001002474

• Genomic_profiling_of_B_other_Adult_ALL_RNA

  Adult ALL is an aggressive leukaemia, affecting adults of all ages. It is associated with a rapid onset and poor outcomes. Our understanding of adult ALL genome has been limited to molecular markers first described in paediatric ALL and validated in adult ALL and to date there have been no studies investigating the genomics of Adult ALL. We will perform whole genome sequencing on at least 100 Adult ALL cases. Priority will be given on ALL cases without a known primary lesion by cytogenetic analysis which are categorised as “B-other”. We will also sequence representative cases of each known subtype. This will deliver a comprehensive annotation of the genomic landscape of Adult ALL to include acquired somatic mutations (substitutions, indels, structural variants/fusion genes) and copy number profiles. The focus on B-other Adult ALL is likely to result in new and previously undescribed genomic lesions.

  Study EGAS00001003428

• AC-ICAM: An Atlas and Compass of Immune-CAncer-Microbiome Interactions in Colon Cancer

  Fresh frozen tumor samples and matched normal colon specimens from chemotherapy naïve, consecutive patients with a histological diagnosis of colon adenocarcinoma at Leiden University Medical Center (LUMC) were subjected to multi-omics profiling at Sidra Integrated Genomics Services, part of Sidra Medicine, Doha, Qatar. This resulted in a high-quality dataset of samples collected between 2001 and 2015. Multi-step QC was performed, including assessment of the quality of the nucleic acid extraction, sequencing, and genetic concordance between DNA/RNA sequences from the same patient. After QC, this resulted in RNA sequencing on 348 tumor samples, whole exome sequencing (WES) on 281 tumor-normal sample pairs (n=562 samples), TCR sequencing of the TCR β locus (TRB) for 114 tumor and 10 matched normal samples, and 16S rDNA sequencing on 246 tumor-normal sample pairs (n=492 samples) and 42 tumor only samples, and 167 WGS non human-aligned reads of the tumor samples. Extensive clinicopathological and survival data of the cohort are available. The median follow-up time for this cohort is 4.6 years, and the distribution of gender and pathological stage are within expected ranges for this patient population with a mean age of 68. We refer to this resource as the Sidra-LUMC (SILU) colon adenocarcinoma (COAD) Atlas and Compass of Immune-Colon cancer-Microbiome interactions (AC-ICAM)."Reprinted from Nature Medicine,Roelands, J., Kuppen, P.J.K., Ahmed, E.I. et al. An integrated tumor, immune and microbiome atlas of colon cancer. Nat Med (2023). https://doi.org/10.1038/s41591-023-02324-5, with permission from Nature."

  Study phs002978

• 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

• Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling (hipo_021)

  Parathyroid carcinoma (PC) is an orphan malignancy with a high risk of recurrence after surgery. Tumor-directed systemic treatments for PC are not established. We used whole-genome and RNA sequencing in four patients with advanced PC to identify molecular alterations that could guide clinical management. In two cases, the genomic and transcriptomic profiles provided targets for experimental therapies that resulted in biochemical response and prolonged disease stabilization: (i) immune checkpoint inhibition with pembrolizumab based on high tumor mutational burden and a single-base substitution signature associated with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) overactivation; (ii) multi-receptor tyrosine kinase inhibition with lenvatinib due to overexpression of FGFR1 and RET and, later in the course of disease, PARP inhibition with olaparib prompted by signs of defective homologous recombination DNA repair. In addition, our data provided new insights into the molecular landscape of PC with respect to the genome-wide footprints of specific mutational processes and pathogenic germline alterations. These data underscore the potential of comprehensive molecular analyses to improve care for patients with ultra-rare cancers based on insight into disease biology.

  Study EGAS00001006747

• Aggressive genomic features in clinicallyindolent primary HHV8-negative effusion-based lymphoma

  Human herpesvirus 8-negative effusion-based lymphoma (HHV8-negative EBL) is a distinct lymphoma entity related to fluid overload states caused by underlying medical conditions. Due to a phenotypical resemblance with secondary effusion of diffuse large B-cell lymphoma (DLBCL), HHV8-negative EBL is easily misdiagnosed. However, in contrast to DLBCL, HHV8-negative EBL follows a mild clinical course, underpinning the importance to differentiate between the two entities. Only limited molecular data of HHV8-negative EBL has been reported and characteristic genomic patterns are lacking. We performed extensive genomic profiling on 8 HHV8-negative EBL cases. A mean number of 33.6 copy number gains and losses per case were found, with recurrent focal deletions of chromosome 3p14.2 and 6q21 in 6/8 cases, encompassing tumor supressor genes FHIT and PRDM1, respectively. We observed a high rate of mutations across genes frequently involved in DLBCL, including patterns of somatic hypermutation. The most abundant hotspot mutation was found in MYD88L265P (3/8 cases). In addition, 5/8 cases had one or more translocations, involving MYC, BCL2, BCL6, TP63, EXOC2 and KMT2D, with Ig and non-Ig partners. We conclude that HHV8-negative EBL is characterized by genomic features that are commonly found in more aggressive B-cell lymphomas, but despite this follow an indolent clinical course.

  Study EGAS00001002743

• Involvement of the FGF8/FGF Receptor Signaling Pathway in the Maintenance and Progression of Fusion-Positive Rhabdomyosarcoma

  In our previous work, we used a myoblast model of fusion-positive rhabdomyosarcoma (FP-RMS) to demonstrate that FGF8, a target of the PAX3-FOXO1 (P3F) transcription factor, is essential for tumorigenicity driven by P3F. When aberrantly expressed, FGF8 can also sustain tumorigenicity in recurrent tumors that are independent of P3F. In this study, we report that FGF8, along with its receptors FGFR1 and FGFR4, is often highly expressed in FP-RMS tumors. We found that high levels of FGF8 expression in FP-RMS cells correlate with increased sensitivity to an FGFR4 inhibitor and a pan-FGFR inhibitor. Conversely, downregulating FGF8 led to a loss of sensitivity to these inhibitors. Interestingly, when FGF8 was upregulated in myoblasts, it resulted in decreased FGFR4 expression and sensitized the cells to an FGFR1 inhibitor and a pan-FGFR inhibitor. The downregulation of FGFR4 expression mediated by FGF8 could be reversed by inhibiting FGFR1, MEK, or ERK, thereby defining a signaling pathway through which FGF8 exerts its regulatory effects. Additionally, we discovered that high FGF8 expression in P3F-independent recurrent tumors is due to a rearrangement of viral long terminal repeat (LTR) sequences into the 3' untranslated region (UTR) of FGF8, leading to increased stability of FGF8 mRNA. These findings indicate that FGF8 plays an oncogenic role in FP-RMS through FGFR4 and may also exert oncogenic effects in P3F-independent relapses via FGFR1. Our study highlights the functional significance of FGF8 in FP-RMS and supports the rationale for preclinical investigations of FGFR inhibitors in treating this type of cancer.

  Study phs004009

• Investigation of MMBIR DNA Repair in Normal and Cancer Human Cells

  Microhomology-mediated break-induced replication (MMBIR) is a DNA repair pathway in which template switching at microhomology was proposed to promote complex genomic rearrangements (CGRs) that contribute to cancer. Yet, the extent of MMBIR activity in genomes is poorly understood due to difficulty in directly identifying MMBIR events by whole genome sequencing (WGS). This study aims to detect MMBIR events in human cancer genomes and to determine their frequency and complexity in tumors as compared to their non-tumor counterparts. This study contains WGS data from matched tumor and normal samples, and cultured cell line control WGS datasets that are not currently represented in other cancer genome databases.

  Study phs002237

• RNAseq from 6 organotypic co-cultures (OC cells bulk/OCSC with or without TME)

  The dataset contains samples of 6 organotypic co-cultures, assembled with patient-derived material from ovarian cancer (OC) patients. Tumor cells, both as bulk and as cancer stem cells-enriched (OCSC) populations, are cultured or not with in vitro peritoneal TME (for details see Battistini C et al, Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness, CDDis 2024). Dataset is composed by fastq file (paired end) type from bulk RNA-Seq.

  Dataset EGAD50000000523