16792 results for "sec+and+unspecified+malignant+neoplasm"

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• Genome-Wide Analysis of Aberrant Position and Sequence of Plasma DNA Fragment Ends in Patients With Cancer

  This study investigated fragmentation characteristics in plasma cell-free DNA and evaluated the relevance of such analysis for cancer diagnostics. Specifically, we performed whole genome sequencing (WGS) of healthy individuals and cancer patients, and evaluated genome-wide coverage and sequences surrounding fragment ends. This was a retrospective study of archived plasma samples. The WGS data are available through this submission. Detailed study design and findings were published in Budhraja et al. Science Translational Medicine 2023.

  Study phs003170

• Longitudinal Assessment of Methylmercury and Gut Microbes During Pregnancy

  Methylmercury is a potent neurotoxin, and the fetal period is the most vulnerable exposure period. There is significant variability in methylmercury metabolism, which has been attributed to differences in the structure and function of the gut microbiome. Our main objective was to better understand the interplay between gut microorganisms and methylmercury metabolism during pregnancy. To address this aim, associations were investigated between maternal biomarkers (blood, hair, stool) for prenatal methylmercury exposure and maternal gut microbiota during early and late gestation.

  Study phs001768

• Single cell targeted DNA-sequencing (and antibody sequencing) of high hyperdiploid B-ALL

  This dataset contains all sequencing data of the publication "Single-cell DNA and Surface Protein Characterization of High Hyperdiploid Acute Lymphoblastic Leukemia at Diagnosis and During Treatment". We provide both the raw fastq-files as well as the processed data in the form of .h5 files. There are 13 patients: XJ176, XH135, XJ180, XI145, XI148, XI167, XI150, XJ175, XJ178, XI162, XF98, XG111 and XG115. Of 9 patients, also follow-up samples during/after treatment were sequenced: XJ180, XI145, XI148, XI167, XI150, XJ175, XJ178, XI162 and XG111. To identify the cell types and distinguish between normal and leukemic cells, cell surface proteins were also captured for 6 samples: XF98, XG111 (at diagnosis and during treatment), XG115, XI162 (after treatment) and XJ175 (after treatment). All samples were processed on the MissionBio platform with a custom amplicon panel, and DaB-seq for the combined targeted DNA and protein sequencing.

  Dataset EGAD50000000829

• Sequencing of serial plasma and multiregional tumor samples in a patient with metastatic breast cancer

  Circulating tumor DNA analysis can be used to track tumor burden and analyze cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here, we follow a patient with metastatic ER and HER2 positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in 8 tumor biopsies and 9 plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing.

  Study EGAS00001001466

• WGS of breast cancer diagnosed during pregnancy and matched control

  The aim of this study was to compare the mutational landscape of breast cancer diagnosed during pregnancy (BCP) and breast cancer from age/stage non-pregnant patients (controls). We present whole genome sequencing data (Illumina HiSeq X ten platform) of tumor and matched normal tissues from 35 BCP patients and 20 controls. This work provides important novel biological insights and a unique resource to study the biology of breast cancer in young women and how pregnancy could modulate tumor biology.

  Study EGAS00001002685

• NHLBI TOPMed: GOLDN Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate

  The GOLDN study was initiated to assess how genetic factors interact with environmental (diet and drug) interventions to influence blood levels of triglycerides and other atherogenic lipid species and inflammation markers (registered at clinicaltrials.gov, number NCT00083369). The study recruited Caucasian participants primarily from three-generational pedigrees from two NHLBI Family Heart Study (FHS) field centers (Minneapolis, MN and Salt Lake City, UT). Only families with at least two siblings were recruited and only participants who did not take lipid-lowering agents (pharmaceuticals or nutraceuticals) for at least 4 weeks prior to the initial visit were included. The diet intervention followed the protocol of Patsch et al. (1992). The whipping cream (83% fat) meal had 700 Calories/m2 body surface area (2.93 mJ/m2 body surface area): 3% of calories were derived from protein (instant nonfat dry milk) and 14% from carbohydrate (sugar). The ratio of polyunsaturated to saturated fat was 0.06 and the cholesterol content of the average meal was 240 mg. The mixture was blended with ice and flavorings. Blood samples were drawn immediately before (fasting) and at 3.5 and 6 hours after consuming the high-fat meal. The diet intervention was administered at baseline as well as after a 3-week treatment with 160 mg micronized fenofibrate. Participants were given the option to complete one or both (diet and drug) interventions. Of all participants, 1079 had phenotypic data and provided appropriate consent, and underwent whole genome sequencing through the Trans-Omics for Precision Medicine (TOPMed) program. Comprehensive phenotypic and pedigree data for GOLDN study participants are available through dbGaP phs000741.

  Study phs001359

• NHLBI GO-ESP: Lung Cohorts Exome Sequencing Project (Asthma): Genetic variants affecting susceptibility and severity

  The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. The exome sequencing asthma project includes 200 African-Americans with asthma from the NHLBI multicenter Severe Asthma Research Program (SARP). SARP participants were recruited at the NHLBI SARP sites with an emphasis on recruiting severe asthmatics (Moore et al., Am J Respir Crit Care Med, 2010. PMID: 19892860). Asthma status was based on both a physician's diagnosis and either bronchodilator reversibility or hyper-responsiveness to methacholine as well as less than 5 pack years of smoking. All subjects were carefully characterized using the standardized SARP protocol which included spirometry (medication withheld), maximum bronchodilator reversibility, hyper-responsiveness to methacholine (not performed in subjects with low baseline FEV1), skin-tests to common allergens, questionnaires on health care utilization and medication use and sputum, lung imaging and bronchoscopy in a subset. In addition GWAS data are available (phs000355, Illumina platform).

  Study phs000422

• Newborn Screening Translational Research Network (NBSTRN): Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT2)

  Large-scale studies of whole genome sequencing (WGS) in neonates have largely been neglected. Thus, the clinical and social implications of this absence are largely unknown. The proposed study aims to increase scientific knowledge for acutely ill neonates. This population may stand to benefit largely from WGS given the severity of illness. The proposed clinical study is a prospective, randomized, partially-blinded study that has both quantitative and qualitative assessments of the risks and benefits of the use of STATseq, a 2-day genome test, in acutely ill neonates at Children's Mercy Hospital. Study participants include neonates, their parents, and clinicians caring for them. The overall aims will provide a nuanced understanding of the role of rapid diagnostic WGS for acutely ill neonates, including relative diagnostic sensitivity and change in management both for broad NICU populations and subpopulations, accuracy, reproducibility, and relative value of proband WGS and familial triads. The technological aims include improving diagnostic sensitivity without sacrificing the rapid turnaround time. The clinical aims include looking at increased diagnostic yield, shorter time to diagnosis and clinician perception of management changes that result from implementation of STAT-seq. Finally, the study will investigate the perceived value of STAT-seq in parents and clinicians using structural equation modeling. The studies also are designed for long-term continuation of assessment of the enrollees (beyond the current funding period) and in additional sample types (via a biorepository). Long-term continuation studies will test effects on long-term morbidity, mortality, quality of life and cost of care. We hope that the study results will be sufficient to provide an evidence base for physician adoption and provider reimbursement of WGS in Level 3 and 4 NICUs.

  Study phs002094

• Bone marrow breakout lesions act as key sites for tumor-immune cell diversification and exhaustion in multiple myeloma

  Multiple myeloma is a disease characterized by the expansion of cancerous plasma cells in the bone marrow. The bone marrow microenvironment plays a pivotal role in supporting myeloma growth and modulating tumor immunity. As the disease progresses, myeloma cells may become independent of the bone marrow environment, leading to extramedullary disease associated with poor prognosis. However, the early processes associated with bone marrow independence and its implications for disease and immune control remain poorly understood. Here, we employed comprehensive single-cell and spatial mapping to identify the disruption of the cortical bone and subsequent expansion of myeloma cells in breakout lesions as a key event in multiple myeloma pathogenesis and tumor immunity. Breakout lesions harbor an adapted niche and a unique immune microenvironment conferred by sustained immune-tumor interactions. In particular, tumor-reactive T cells with a highly exhausted phenotype, alongside unique NK cell and macrophage subtypes, specifically expanded in breakout lesions. Spatially-resolved genomic, transcriptomic and cellular analyses uncovered extensive intra-lesion heterogeneity, suggesting a divergent co-evolution of genomic variation and locally confined T cell responses in distinct subregions. Ultra-high plex imaging revealed that tumor-reactive T cells, together with other immune-regulatory cells and dendritic cells, co-expand and exhaust upon sustained tumor interactions in locally confined immune islands. In contrast, immune-regulatory macrophage and NK cell subsets operate spatially separated within myeloma cell deserts. Jointly, our analyses uncover bone marrow breakout lesions as a hotspot for tumor-immune cell interactions, diversification and exhaustion, representing a key event in myeloma pathogenesis with significant therapeutic implications.

  Study EGAS50000000304

• Influence of age on molecular changes and treatment stratification in multimodal glioblastoma therapy

  Background: The increasing life expectancy has led to a rise in high-grade gliomas, particularly in patients of older age. The impact of chronological age, associated molecular changes and contributing factors on therapy response, progression-free survival (PFS) and overall survival (OS) remain uncertain. Methods: Between January 1st, 2016, and December 31th, 2021, patients with glioblastoma IDH-wt (CNS WHO grade 4) were included. RNA- and T-cell receptor sequencing was performed in a subset of patients. Primary outcome parameters were extent of resection (EOR), progression free- and overall survival. Multivariate analysis was performed to identify independent predictors of survival. Results: A total of 286 patients were included. The mean age was 66.4 years. Chronological age did not correlate with overall survival (r=0.12). With age, tumor immune composition changed towards macrophages with M2 phenotype and decreased numbers of CD8+ and neutrophiles. Aging related genes were not enriched. Beyond 69.5 years of age, despite similar PFS (p=0.0783), OS (p<0.0001) was significantly shorter, compared to younger patients. Extent of resection and adjuvant radiochemotherapy were significant predictors of OS (p<0.0001). No difference in PFS and OS was found between younger and older patients treated with maximal safe resection, followed by concomitant RT and chemotherapy and adjuvant chemotherapy. Conclusions: This study suggests that age alone should not be the sole determinant in therapeutic decision-making for glioblastoma patients. Gross total resection and adjuvant therapy, tailored to individual clinical status, significantly impact survival outcomes. Patient-specific treatment strategies are important to minimize undertreatment and optimize therapeutic outcomes in older patients.

  Study EGAS00001008246