Search Results - EGA European Genome-Phenome Archive

Childhood Cancer Data Initiative (CCDI): CCDI Pediatric In Vivo Testing Program - Orthotopic CNS Tumors

The goal of this project is to advance the development of effective therapies for pediatric brain cancers through preclinical in vivo testing of novel agents. We utilize a well-characterized panel of approximately 150 patient-derived orthotopic xenograft (PDOX) models that replicate the histopathologic and molecular features of the original patient tumors. These models represent multiple pediatric CNS tumor types, including high-grade glioma, medulloblastoma, ependymoma, diffuse intrinsic pontine glioma (DIPG), and atypical teratoid/rhabdoid tumor (ATRT), across diverse disease stages and molecular subtypes. As part of this effort, the PDOX models are being molecularly characterized to identify promising therapeutic candidates. Molecular profiling includes whole exome sequencing (WES), RNA-seq, MethylEPIC array, CytoSNP array, and DNA fingerprinting for quality control. Demographic and clinical data (e.g., diagnosis, disease site, disease status) are also shared.

Study phs003162

Radiology Imaging Data Containing Faces from The Cancer Imaging Archive

Effective January 6, 2022, all radiology datasets containing images that could be used to reconstruct a 3D volume resembling a human face were put behind a controlled-access request system to mitigate potential re-identification risks emerging from advances in facial recognition tools.

Study phs004225

Impact of HLA Aberrations on Tumor Neoepitope Presentation

TP53 mutations may encode tumor-specific truncal neoantigens for targeting cytotoxic T lymphocyte (CTL). Using mass spectrometry followed by X-ray crystallographic analysis of HLA-bound p53 neoantigens, clinical tumor database analyses, and functional studies of neoantigen-directed T cell receptors (TCRs), we have built a comprehensive p53 immunopeptidome. As a component of this study, we noted that tumors with neoantigens displayable on HLA-A*02:01 or HLA-B*07:02, and structurally divergent from p53 wild-type peptide-HLA complexes, may exploit an allele's absence for growth in patients. The data deposited highlights that in brain metastasis of an ovarian cancer, that a damaged HLA-A*02:01 allele resulted in inability to present the p53 I195F neoepitope (GLAPPQHLFRV). Conversely, a simultaneously processed glioblastoma sample, sequenced as a control (and bearing a p53 R248W mutation on an A*24:02/A*32:01 background), revealed full exome genomic reads and transcript reads of the HLA-A locus. This indicated that biallelic HLA-A loss in the 10-417-1023 tumor was not a technical issue but represented damage to the 5' encoding exons of HLA-A.

Study phs004529

NCTN_NCORP: Phase III Trial of LHRH Analog Administration During Chemotherapy to Reduce Ovarian Failure Following Chemotherapy in Early Stage, Hormone-Receptor Negative Breast Cancer (S0230)

Study ID: S0230NCT Number: NCT00068601 SWOG Cancer Research NetworkSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN_NCORP: Phase III Trial of LHRH Analog Administration during Chemotherapy to Reduce Ovarian Failure following Chemotherapy in Early Stage, Hormone-Receptor Negative Breast Cancer (S0230)Trial Description: RATIONALE: Goserelin blocks hormone production in the ovaries. It is not yet known whether ovarian suppression using goserelin will prevent ovarian failure (early menopause) in women receiving chemotherapy for breast cancer.PURPOSE: This randomized phase III trial is studying how well giving goserelin together with chemotherapy works compared with chemotherapy alone in preventing early menopause in women with stage I, stage II, or stage IIIA breast cancer. Clinical data presented in the following publication(s):PMID 25738668Disease type(s): Breast Neoplasm - Breast Cancer - InvasiveClinical Dataset(s) included:NCT00068601-D1 (PMID 25738668): There is one dataset for S0230's primary publication 25738668. This dataset contains baseline characteristics, planned chemotherapy regimen, hormone receptor status, premature ovarian failure, fertility, survival, ovarian failure, and adverse event data.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004261

Healthy Communities Study (HCS-BioLINCC)

Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Objectives: To examine the relationships between characteristics of community programs and policies that are designed to prevent childhood obesity and are focused on Body Mass Index, diet, and physical activity in children.Background: Childhood obesity is a major public health issue in the U.S. with 18.5% of children aged 2-19 having obesity (Hales, Caroll, Fryer, and Ogden, 2017). Children who have obesity are more likely to have cardiovascular risk factors (Freedman, Mei, Srinivasan, Berenson, & Dietz, 2007; Koskinen et al., 2018), type 2 diabetes (Goran, Ball, & Cruz, 2003) and are at increased risk for morbidity and mortality as adults (Reilly & Kelly, 2011) including increased risk of developing several types of cancer (World Cancer Research Fund/American Institute for Cancer Research, 2007).Community programs and policies targeting childhood obesity are being implemented across the country, but their approaches have not been systematically studied. There is natural variation in many aspects of community programs and policies, including intensity level, duration, funding, target population, and how they are implemented. However, no previous studies have examined these variations and how such aspects of community programs and policies are related to childhood obesity outcomes. The Healthy Communities Study (HCS) was initiated to address the need for a study of community programs and policies and their relationship with childhood obesity.The three aims of HCS are to: 1) determine the associations between characteristics of community programs and policies and obesity outcomes in children; 2) identify factors that modify or mediate the associations; and 3) examine the association between characteristics of program and policies and obesity outcomes in communities that have a high proportion of African American or Hispanic residents. This study was not designed to evaluate any one specific program, policy or community, but was designed to systematically assess if components or characteristics of programs/policies in communities across the country are related to BMI, diet, and physical activity in children.Design: Community selection: For the purposes of HCS, a community was defined as a high school catchment area, and child participants were students at public elementary and middle schools (kindergarten through eighth grade) within the catchment areas. Communities were selected using a hybrid sampling approach. Some of the communities were “certainty” communities, which had implemented promising program and policies targeting childhood obesity. Other communities were sampled using a stratified national probability-based sample, using weights proportional to the number of children aged 4-15 in each Census Tract.Participant recruitment At the school level, children were recruited from two public elementary and two public middle schools in each community. Materials were distributed to children in these schools and families who completed the forms were contacted by the study.The HCS employed a complex study design that included a diverse sample of communities across the country and combines current/cross-sectional and retrospective data. Data were collected at multiple levels including at the child/household, schools, and community levels.Cross-sectional component: Interviews conducted in households along with community and school assessments were the primary data collection activities for HCS. Cross-sectional data were collected on a) children and their families, b) schools, and c) communities:a. Children and households: All children participated in the Standard Protocol measure consisting of: medical history, height, weight, and waist circumference measurements of the child; height and weight measurements (or self-reported measurements) of the two parent(s)/caregiver(s); general demographic and background questions; brief nutrition and physical activity behavior questionnaires; and a modified Windshield Survey of the home. A subset of children (approximately 14% of the children in the 130 communities) received an Enhanced Protocol, which included: all of the Standard Protocol measures listed previously plus (2) 24-hour dietary recalls during both of the home visits, the use of an accelerometer for a one-week period between the first and second home visit, and a previous day physical activity assessment questionnaire at the end of the second visit.b. Schools: School assessments were comprised of web-based surveys and observations of the 4 participating schools. Observations in the 2 elementary and 2 middle schools included lunchroom observations, an interview of the physical education instructor, and a Physical Activity Resource Assessment (PARA) was administered to observe the school's outdoor physical activity resources. Web-based surveys were administered to the district food service administrator/manager and a staff member from each school. The school staff completed a survey on school policies and practices related to physical activity and nutrition, whereas, the district –level personnel completed a food environment questionnaire for each of the recruited schools that were in their district.c. Communities: In each community, interviews were conducted with key informants (10-14 persons per community) to review and gather characteristics on current community policies and programs and for communities programs and policies for up to 10 years prior.Retrospective component:a. Among children, medical records were abstracted for going back up to 10 years in approximately 65-70% the sample to develop longitudinal BMI trajectories.b. Communities: Data were collected from key informants in each community on characteristics of programs and polices going back up to 10 years to assess how programs and policies unfolded over time in each community.Demographics:Communities: A total of 130 diverse communities participated in the HCS. Communities were diverse with respect to low income (38.5%), urbanicity (38.5% urban, 38.5% suburban, 23.1% rural), and geographic region (42.3% South, 22.3% West, 20% Midwest, 15.4% Northeast). Communities with a high proportion of race-ethnic groups also were oversampled (32.3% Hispanic, 26.2% African American, 41.5% other). Data were collected in a total of 436 schools; 227 elementary (52%), 53 elementary/middle (12%), and 158 middle schools (36%).There were 1,421 key informants interviewed across the 130 communities. Through the key informant interviews and document abstraction, 9,681 community programs and policies (CPPs) over the ten year retrospective study period were identified and characterized.Participants: A total of 5,138 children and their parent(s)/caregiver(s) from 130 diverse communities across the country were recruited for the HCS study. Child participants were evenly distributed across ages 4–15 years and gender; 21.5% were African American and 43.5% were Hispanic. Nearly a third of households reported an annual income below $20,000.

Study phs004494

Cellular and Molecular Profiling of Epithelial Ovarian Cancers and Associated Normal Tissues

This collection of data includes bulk RNA-seq and whole genome bisulfite sequencing (WGBS) for ovarian cancer samples (microdissected into carcinoma and stroma compartments), as well as single-cell RNA-seq (scRNA-Seq) and bulk WGBS and enzymatic methyl-seq (EM-seq) normal human Fallopian tube samples. The data from the ovarian cancer samples was collected to understand cellular and molecular alterations associated with histological and molecular subtypes of ovarian cancer. Data for these samples are included in Djirackor, Heinze et al. (accepted at Cancer Research). The scRNA-Seq data was generated to identify the developmental trajectory, cell type composition, and point towards the cell-of-origin for high grade serous ovarian carcinoma (HGSOC). Further, this was intended to establish a normal RNA reference for the cancer data. Results from this study are described in Johnson, Majewski et al. (accepted at Nature Communications, preprint PMID: 40475517). The data from bulk DNA methylation on normal Fallopian tubes was used to optimize the bisulfite-conversion process for the cancer samples and to serve as an epigenetic reference in the cancer studies. This data is described in Morrison et al. (PMID: 34147133). Any questions can be directed to Hui Shen (hui.shen@vai.org).

Study phs004702

Kids First: Genomics of Isolated Cleft Lip

Isolated Cleft Lip (CL, Human Phenotype Ontology # HP0100335) is a subtype within Orofacial Clefts (OFC, HP0000202) birth defects. OFCs can involve gaps in the lip, alveolus and/or the hard or soft palate. Developmental origins of the affected structures, epidemiology, and familial patterns of CL versus other OFCs suggest some common risk factors, but emerging evidence emphasizes that these subtypes also have unique risk factors. Isolated CL has seldom been investigated separately in genetic studies. Early studies using microsatellite markers prior to the availability of SNP chips found differences in CL families versus other cleft subtypes, notably reporting increased association with certain IRF6 variants in CL families versus other cleft types. With the advent of SNP chips, some studies addressed CL, e.g. genome-wide association of CL was seen with TPM1 and NOG and 9q21.32. We have performed some of the only genome-wide association studies (GWAS) to compare and contrast CL and Cleft Lip with Cleft Palate (CLP). We find evidence that CL and CLP have some distinct genetic risk factors, differences in strength or direction of effects between CL and CLP, and modifying loci that predispose specifically for CL over CLP. Some loci are most-significant in families where all affected members had CL. Modifiers of cleft lip laterality and side of the cleft were more successful in CL than in CLP and the loci identified in CL had no detectable effect in CLP, reinforcing the idea that CL and CLP have distinct risk factors. An overall conclusion from these studies is that CL appears more genetically homogeneous than does CLP, thus highlighting the importance of subtype and family type inclusion in studies of OFCs. Importantly, the homogeneity of CL makes it more amenable to gene discovery in the moderate sample sizes available with whole genome sequencing (WGS). The current project builds upon the GWAS and WGS analyses by our group and others. The WGS data generated will be used to discover new loci for CL, to replicate/prioritize previously published loci, and to aid in determining CL-specific causal genes/alleles. Short Read WGS data available for 1903 individuals include 629 affected probands: 553 CL and 40 CLP (with CL relatives) complete trios, 29 CL and 1 CLP dyads, and 5 CL and 1 CLP singletons. Of the 1903 total individuals, 554 are of European descent, 381 Central/South American descent, 857 of Asian descent, 7 of African descent, and 104 are race other/unknown. With our phenotypic data plus the WGS, we will be able to find new loci, gain better understanding of how risk related to those loci differs across populations, create the knowledge needed to choose loci for follow-up functional studies, build the knowledge needed for accurate risk predictions, and ultimately set the stage for translation into clinical practice. Study Population: The individuals and families utilized in this project were recruited through the Pittsburgh Orofacial Cleft study (POFC) involved research collaborations world-wide coordinated by the Center for Craniofacial and Dental Genetics of the University of Pittsburgh (CCDG). Extensive information is available for many of these trios, including sex, self-reported race and ethnicity, birth date and age at enrollment, phenotypes for affected cases (i.e. extensive detail on the OFC defect in terms of type, laterality, completeness), phenotypes for all affected and unaffected family members (including facial measurements, lip morphology, dental characteristics and many more), vital status and age at last known vital status, clinical information (e.g. surgical and medical history for all affected cases, some limited systems review for unaffected family members), and family medical history (e.g., family history of cancer and birth defects).Molecular Technology: Short Read WGSData Available: Demographics (site, age, sex, race, ethnicity) Cleft details Family level cleft details (i.e. multiplex, clefting maternal side, clefting paternal side, or both) Height/Weight Pregnancy Exposures data (birth height, birth weight, smoking, vitamins, alcohol, epilepsy, gestational diabetes) for 3 months prior to first trimester and first trimester. Subject_IDs from other sequencing studies Data use limitations from the consents The remaining phenotypic/medical/image data for this study are available through FaceBase (facebase.org): DOI: 10.25550/5A-FJBJ and DOI: 10.25550/56-ES6P.

Study phs003893

Blood and Marrow Clinical Trials Network Trial of Non-Myeloablative Conditioning and Transplantation of Umbilical Cord Blood For Hematologic Malignancies (BMT CTN-0604-BioLINCC)

Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.Objectives: To examine the safety and effectiveness of a non-myeloablative stem cell transplant using umbilical cord blood as a treatment option for patients with leukemia or lymphoma and no suitable related donor.Background: Chemotherapy is a common treatment option for patients with aggressive forms of the blood cancers leukemia and lymphoma, but other treatment methods may need to be considered if the cancer does not respond well to chemotherapy, or if the cancer returns. In such cases, it may be recommended that the patient receive a stem cell transplant, commonly using donated bone marrow. A first degree relative is likely to be the best candidate for donation if the human leukocyte antigen (HLA) markers are a sufficient match. For patients lacking a HLA-matched related donor, it is routine to initiate an unrelated donor search. However some patients, particularly ethnic minorities, experience disease progression while awaiting identification of a suitably HLA-matched donor. Recently, stem cell transplants using umbilical cord blood have become a viable alternative option to treat these types of cancers.Typically patients undergoing a stem cell transplant receive high doses of chemotherapy before the transplant to prepare their bodies to accept the donor stem cells. In this study, participants received a type of stem cell transplant called a non-myeloablative transplant, which is a reduced intensity conditioning (RIC) method of transplantation that does not require high doses of chemotherapy. RIC can be preferable in patients that are older and less clinically fit, and therefore less able to withstand the chemotherapeutic agents' toxicity levels.The BMT CTN 0604 study was one of two parallel multicenter phase 2 studies; the other of which was BMT CTN 0603, which used partially HLA-mismatched related bone marrow (Haplo-marrow) transplantation. The goal of these studies was to generate pilot multicenter data to support a future phase 3 randomized clinical trial.Participants: Patients less than 71 years of age with acute leukemia or lymphoma and lacking a suitable HLA-matched related donor were eligible to participate. Patients less than 22 years of age were eligible if they were ineligible for the BMT CTN 0501 trial. Acute leukemia was required to be in morphologic complete remission. Large-cell, mantle-cell, and Hodgkin lymphomas were required to have achieved at least a partial remission with treatment before allogeneic hematopoietic cell transplantation. Low-grade lymphoma patients were required to have failed two prior chemotherapy regimens. Patients who had undergone prior autologous transplantation were not excluded as long as three months had elapsed since the procedure. Participants were also required to have adequate organ function, including a left ventricular ejection fraction of at least 35% and specific liver, kidney, pulmonary, and physical functioning scores within acceptable ranges. A total of 54 individuals were enrolled in the study and 50 were included in the analysis.Design: Participants underwent a reduced intensity conditioning regimen prior to receiving the double umbilical cord blood (dUCB) transplant, which included two chemotherapeutic agents, cyclophosphamide and fludarabine, and a small dose of radiation. Cyclophosphamide was administered intravenously at 50 mg/kg six days before the transplant. Fludarabine was administered intravenously at 40 mg/m2 (adjusted for creatinine clearance) each day for five days before the transplant. A single dose of 200 cGy total body irradiation was performed one day prior to transplantation. Participants also received cyclosporine and mycophenolate mofetil (MMF) beginning three days before the transplant as prophylaxis for graft-versus-host-disease (GVHD). Participants could receive tacrolimus instead of cyclosporine.At transplantation, patients received two partially HLA-matched umbilical cord blood units from unrelated donors. The maximum allowable mismatch between the UCB unit and the recipient, or between the UCB units, was 2 of 6 HLA loci. Each unit contained a minimum of 1.5 × 107 nucleated cells, or 2.0 × 107 for units that were not red cell depleted, per kilogram of recipient weight. Units were thawed and infused per institutional practice after validation using methods approved by the study. After transplantation, filgrastim, a granulocyte-colony stimulating factor, was initiated at 5 μg/kg a day and continued until the absolute neutrophil count was at least 2000/μL for three consecutive days. Participants continued to receive MMF for 30 days after the transplant or 7 days after engraftment, whichever was later, and cyclosporine or tacrolimus until 180 to 200 days after the transplant. Supportive care, including blood product administration, prophylaxis, therapy for infection, and treatment of GVHD, was at the discretion of treating physicians and transplantation center practices.The primary outcome was participant survival from the time of transplant to 180 days. Secondary end points included progression-free survival and cumulative incidences of hematopoietic recovery, acute or chronic GVHD, relapse, and non-relapse mortality.Conclusions: Survival at 180 days after double umbilical cord blood transplant was 74%. Collectively, the results of BMT CTN 0603 and 0604 confirm the utility of dUCB and Haplo-marrow as alternative donor sources for reduced intensity conditioning hematopoietic cell transplantation, providing a rationale for an additional clinical trial to assess the relative efficacy of these two strategies.

Study phs004890

Cardiovascular Cell Therapy Research Network - A Phase I, First-in-Human, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Allogeneic Mesenchymal Stem Cells in Cancer Survivors With Anthracycline-Induced Cardiomyopathy (CCTRN-SENECA-BioLINCC)

Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.Objectives: To examine the safety and feasibility of delivering allogeneic human mesenchymal stem cells (allo-MSCs) by transendocardial injection to cancer survivors with left ventricular (LV) dysfunction secondary to anthracycline-induced cardiomyopathy (AIC).Background: Anthracycline-based chemotherapies are effective in treating various forms of cancer. The risk of anthracycline-induced cardiomyopathy (AIC) has been primarily related to the lifetime cumulative dose and every exposure to an anthracycline carried some risk of inducing cardiac dysfunction. Historically, AIC has been irreversible with poor prognosis and most prevalent in young persons and females. Previous studies have determined that patients with AIC have approximately 3.5-higher relative risk of death within 5 years compared to ischemic or nonischemic cardiomyopathy. There is currently no effective treatment for AIC.There are several shared pathological features between AIC and heart failure (HF). A promising approach to treatment of HF is the administration of bone marrow–derived mesenchymal stromal cells (MSCs). The SENECA trial was the first-in-human study of allo-MSCs in patients with LV dysfunction secondary to AIC.Participants: Male and female cancer survivors aged 18 to 79 years, with a diagnosis of AIC, were recruited for the SENECA trial. Inclusion criteria included: initial diagnosis of AIC at least 6 months prior to consent; left ventricular ejection fraction (LVEF) ≤45%; receiving stable, optimally tolerated therapy with beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and/or aldosterone antagonists unless contraindicated; no evidence of ischemic heart disease; cancer-free for at least 2 years with a low likelihood of recurrence (a 5-year risk of recurrence estimated at ≤30%).Participants were excluded for any condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up.Design: The primary objectives of SENECA were the safety of allo-MSC administration, the feasibility of delivering the cells to the subjects, and collecting outcome measures. The secondary objectives were to determine the effects of allo-MSC administration on LV function and functional status from baseline to 6 months and from baseline to 12 months after treatment.The trial was initiated with a 6-subject, open-label lead-in phase. Between September 2016 and December 2016, 6 candidates consented to participate and received 20 transendocardial, electromechanically-guided injections of allo-MSCs. A complete safety report of the 6 subjects was provided for review by the data safety monitoring board and FDA. Subsequently, the study was allowed to proceed to the randomization phase.Baseline evaluations to determine eligibility included: cardiac magnetic resonance imaging (CMR), 6-min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ), and a comprehensive laboratory panel that included N-terminal pro-brain natriuretic peptide (NT-proBNP).Between March 2017 and October 2018, 31 eligible subjects were randomized 1:1. There were 14 subjects enrolled in the treatment arm and 17 subjects in the placebo arm. Participants received either 1 × 108 allo-MSCs in 8 ml of Buminate 5% solution or a placebo (8 ml of cell-free Buminate solution) delivered via 20 transendocardial injections (0.4 ml each).All subjects were followed for 1 year, with evaluations at: day 0 (day of injection), day 1, day 7, day 30, day 180, and day 365. A physical examination, electrocardiogram, and laboratory evaluations were conducted at each visit, along with the assessment of adverse events and review of medications. In addition, at 6 months and 1 year, subjects performed the following tests: 6MWT, MLHFQ, and CMR. Serum samples were collected at baseline and 1, 6, and 12 months after treatment to determine whether there were any significant changes in panel reactive antibody (PRA).Conclusions: The SENECA trial demonstrated that allo-MSCs are well-tolerated and that transendocardial injections of allo-MSCs are feasible in patients with AIC. Although the SENECA trial was not designed to test efficacy, a subset of participants was included in secondary endpoint analysis. The only statistically significant differences observed were with the MLHFQ and 6MWT assessments which favored the intervention. Larger studies will be required to determine the efficacy of allo-MSCs treatment.

Study phs004712

BTC GBM TeamLab Trial 1: Longitudinal Tissue Profiling of Recurrent Malignant Glioma During Repeat Dosing of Oncolytic Viral Immunotherapy (NCT03152318)

The data in this repository is generated from the work of the GBM TeamLab as part of Break Through Cancer (BTC) (https://breakthroughcancer.org/). The TeamLab's goal is to evaluate the feasibility, safety, and value of performing serial brain biopsies to obtain biological readouts during the assessment of novel glibolastoma (GBM) therapeutics. The first investigational agent studied by the TeamLab is a novel oncolytic viral immunotherapy (agent: CAN-3110, also known as rQNestin34.5v.2) which was delivered via repeated intratumoral delivery at up to 6 timepoints over a 4-month period in recurrent IDH-wild type GBM patients. Biopsy tissues, blood, and CSF were collected and subjected to multi-omic profiling at each surgical timepoint. This work is being conducted as one of the trial arms for NCT03152318. Controlled access omic data from this study will be deposited here as the results are published.

Study phs004189

8431 results for "canc*"

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