Search Results - EGA European Genome-Phenome Archive

Molecular Characterization of the Immunological Landscape in Human Brain Tumors

We are performing a comprehensive cellular and molecular characterization of the immunological landscape of human brain tumors. This work includes single-cell RNA and T cell receptor (TCR) sequencing of T cells isolated from the tumor and blood of patients with advanced primary (high-grade glioma) and metastatic (non-small cell lung cancer) cancers. Whole exome sequencing on tumor and normal tissue was also performed.

Study phs004853

Pursuing Molecular Biomarkers to Guide Adjuvant Therapy for HPV+ Head and Neck Cancers After Transoral Robotic Surgery

Human papillomavirus-positive oropharyngeal squamous cell carcinomas (HPV+ OPSCCs) represent a distinct subset of head and neck cancers that are rapidly increasing in incidence. Despite the generally favorable prognosis of HPV+ OPSCCs, compared to HPV-negative counterparts, due to higher treatment responsiveness and improved survival, a subset of patients experiences disease recurrence, leading to poor clinical outcomes. The identification of high-risk patients through molecular stratification could enable personalized therapeutic strategies, including intensified treatment or novel interventions. This study focuses on the molecular profiling of treatment-naïve primary HPV+ OPSCCs, aiming to identify molecular characteristics associated with tumor recurrence. In this study, we compared molecular profiles of primary tumors that recurred with those of non-recurrent control tumors to uncover key molecular features linked to recurrence.

Study phs003889

Kids First: Genomic Analysis of Pediatric Rhabdomyosarcoma

The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the genomic and phenotypic data from this study are accessible through dbGaP. The data is also available at the Kids First Portal, where other Kids First datasets can also be accessed in the cloud for data analysis, data visualization, collaboration and interoperability, open to all researchers and developers. Rhabdomyosarcoma (RMS) is one of the most common and deadly sarcomas in children and adolescents, but very little is known about its genetic epidemiology. This study will explore the role of new (i.e., de novo) mutations in both known cancer predisposition genes and novel susceptibility genes on the risk of RMS. A better understanding of the genetic risks for RMS may lead to prevention strategies, better risk stratification, and even the identification of new therapeutic targets.

Study phs004306

Improved Cardiovascular Risk Reduction to Enhance Rural Primary Care (ICARE-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 evaluate whether a centralized, remote clinical pharmacy service could improve guideline adherence and secondary measures of cardiovascular risk in primary care offices in rural and small communitiesBackground: More than 2200 Americans die of cardiovascular disease every day. Team-based care and medication therapy management have become useful strategies to reduce gaps in the delivery of guideline-concordant therapy for cardiovascular therapy. Physician offices, especially in rural and smaller communities, lack the resources to implement team-based care with pharmacists who can provide medication therapy management. The ICARE trial developed a physician-pharmacist collaborative model to provide virtual clinical pharmacy services from a central location to 12 family medicine offices in Iowa to evaluate whether a centralized, remote clinical pharmacy service could improve outcomes.Participants: Subject inclusion involved 3 separate processes. First, subjects were required to be an English-speaking male or female over the age of 50 who had been seen in the clinic/practice at least once in the past 24 months. Second, subjects were required to have at least one of the following conditions: uncontrolled diabetes (hemoglobin A1c > 7.5%); low-density lipoprotein cholesterol (LDL-C) > 110 mg/dl for patients with a history of peripheral artery disease, coronary artery disease, stroke, transient ischemic attack, or diabetes, elevated blood pressure with systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg in persons with diabetes or chronic kidney disease, or systolic BP ≥ 150 mmHg or diastolic BP ≥ 90 mm Hg in persons with uncomplicated hypertension. Third, subjects were required to additionally have three or more of the following cardiovascular conditions or risk factors: history of myocardial infarction, coronary artery disease, stroke, transient ischemic attack, atrial fibrillation, peripheral vascular disease/claudication, current smoker, or obesity with BMI > 30.Exclusion criteria included diagnosis of primary pulmonary hypertension, a cancer diagnosis with a life expectancy of less than 2 years, residence in a nursing home or diagnosis of dementia, no telephone access or a hearing impairment that prevented telephone use, or patient had plans to move from the area or transfer care to a different clinic in the next 12 months.In total, there were 302 subjects enrolled in the ICARE trial. Of these, 259 subjects completed the 12-month visit.Design: The study included 11 private physician offices and one Federally Qualified Health Center. Offices were identified from the Iowa Research Network and screened for their ability to conduct the trial, enroll subjects, and meet quality control measures. A Study Coordinator employed in each office identified, screened, and recruited subjects. All subjects and physicians in a given office received either the intervention or usual care.Blood pressure, hemoglobin A1c, and LDL cholesterol were collected at baseline and 12 months regardless of whether the subject had a diagnosis of hypertension, diabetes, or hyperlipidemia. Baseline data were collected on case report forms by Study Coordinators and entered centrally by the research team.Three clinical pharmacy specialists located within the research offices of the principal investigator provided the intervention. Pharmacists were required to have a Doctor of Pharmacy degree and a minimum of one year of clinical residency (or equivalent practice experience). The pharmacists travelled to each intervention office to be introduced to the providers and facilitate team-building before the intervention started. These sessions explored the providers' preferred methods and frequency of communication with the pharmacists based on other telemedicine studies. Pharmacists had access to the baseline data, including BP and laboratory values, which they used to reconcile medications and update the medical records. Pharmacists monitored blood glucose values, BP readings, laboratory values, and potential adverse events from the EMR or from the patient in order to recommend medication changes to the treating medical provider. Interventions for physicians were directed at improving guideline adherence for reducing CV risk and preventive care based on the Guideline Advantage (GA) criteria.Each subject was assigned to one of the three pharmacists to maintain continuity. Subjects were assigned to the pharmacists in the order they were enrolled into the study, independent of medical office. Subjects were primarily contacted by telephone and counseled by the pharmacists about beneficial health behavior changes related to tobacco use, diet, physical activity, and alcohol consumption. Medications and dosages were reconciled. The pharmacists identified problems related to poor disease control, subject misunderstandings, poor medication adherence or failure to receive preventive health services, adverse effects, drug interactions, and cost. Pharmacists provided patient education when problems were identified and developed a plan for follow-up contacts, generally every 1-2 weeks by telephone if there were continuing problems or medication issues. The primary outcome measure was adherence to the GA criteria.Conclusions: There was no improvement in the GA score from baseline to 12 months in the control group. There was a statistically significant improvement in the intervention group in the GA score plus several criteria were significantly better for intervention subjects including appropriate statin therapy, body mass index (BMI) screening and alcohol screening. Only 13.7% of subjects with diabetes had hemoglobin A1c at goal at baseline and this increased to 30.8% and 21.0% in the intervention and control groups, respectively, at 12 months.The improvements in outcomes were modest and not statistically significant, due to higher-than-anticipated baseline guideline adherence and greater inter-office variability than anticipated.

Study phs004679

GENomics of CAncer DisparitiEs (GENCADE)

Genetic ancestry-concordant RNA splicing events in men with prostate cancer (PCa) involve cancer promoting genes and associate with disease recurrence after radical prostatectomy. Patients diagnosed with PCa who were scheduled to undergo radical prostatectomy or biopsy were enrolled in the GENCADE study, according to the Institutional Review Board (IRB)-approved protocol Pro00053535 (NCT02229565). With respect to NCT02229565, the descriptors “African American” and “Caucasian American” refer to the same patients described as “Black” and “White”, respectively, herein. Patients were also co-enrolled to the Duke BioRepository & Precision Pathology Center (BRPC) protocol (Pro00035974) to facilitate tissue collection.

Study phs003731

GU16-257: Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients with Muscle-Invasive Bladder Cancer with Selective Bladder Sparing

This is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to define the role of clinical complete response (cCR) in predicting benefit in patients opting to avoid cystectomy. Primary Objectives Determine the cCR rate with gemcitabine, cisplatin, plus nivolumab;Determine the ability of cCR (cT0 or cTa) to predict benefit from treatment. Benefit was defined as, among the patients achieving a cCR, either being (a) 2-year metastasis-free in patients forgoing immediate cystectomy or (b) FindingsSeventy-six patients were enrolled; of these, 33 achieved a cCR (43%, 95% confidence interval (CI): 32%, 55%), and 32 of the 33 who achieved a cCR opted to forgo immediate cystectomy. The positive predictive value of cCR was 0.97 (95% CI: 0.91, 1).

Study phs003372

NCTN: A Phase III Randomized Study of Nivolumab Plus Ipilimumab versus Nivolumab for Previously Treated Patients with Stage IV Squamous Cell Lung Cancer and No Matching Biomarker (Lung-Map Sub-Study) (S1400I)

Study ID: S1400INCT Number: NCT02785952SWOG Cancer Research NetworkSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Phase III Randomized Study of Nivolumab plus Ipilimumab versus Nivolumab for Previously Treated Patients with Stage IV Squamous Cell Lung Cancer and No Matching Biomarker (Lung-Map Sub-Study) (S1400I)Trial Description: This randomized phase III trial compares nivolumab with ipilimumab and nivolumab alone in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a "non-match" sub-study that includes all screened patients not eligible for a biomarker-driven sub-study. Monoclonal antibodies, such as nivolumab and ipilimumab, may be able to shrink tumors. It is not yet known whether nivolumab works better with or without ipilimumab in treating patients with squamous cell lung cancer. Clinical data presented in the following publication(s):PMID 34264316 Disease type(s): Lung, Mediastinal and Pleural Neoplasm - Non-Small Cell Lung CancerClinical Dataset(s) included:NCT02785952-D1 (PMID 34264316): There are three datasets (-D1 through -D3) for PMID 34264316, a primary publication for S1400I. This clinical dataset, NCT02785952-D1, contains patient-level data (one row per patient), including baseline, demographic, metastatic sites, and treatment information. It also contains assessment, survival, reasons for going off treatment, tumor mutational burden, PDL1 expression, and patient-reported outcome data.NCT02785952-D2 (PMID 34264316): There are three datasets (-D1 through -D3) for PMID 34264316, a primary publication for S1400I. This toxicity dataset, NCT02785952-D2, contains event-level data (one row per patient per adverse event experienced on trial).NCT02785952-D3 (PMID 34264316): There are three datasets (-D1 through -D3) for PMID 34264316, a primary publication for S1400I. This dataset, NCT02785952-D3, contains biomarker data (one row per patient per gene alteration).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 phs004242

CDK2 Inhibition Demonstrates RB-Independent Efficacy in CDK4/6 Inhibitor-Resistant HR-Positive/HER2-Negative Breast Cancer

Preliminary clinical data from hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative metastatic breast cancer (MBC) patients with resistance to CDK4/6 inhibitors treated with the CDK2 inhibitor PF-07104091 as monotherapy indicate that therapeutic efficacy correlates with TP53 status, but not with RB expression or phosphorylation. Using a panel of HR+/HER2- MBC patient-derived (PD) cell lines, including both CDK4/6 inhibitor-naïve and resistant models, we found that CDK2, unlike CDK4/6, is dispensable for RB phosphorylation. Notably, in models derived from tumors that had progressed on CDK4/6 inhibitor therapy, as well as in models with acquired in vitro resistance, CDK2 inhibition reduced DNA replication rate, induced DNA damage, and inhibited mitotic entry in an RB-independent manner. Data available through this dbGaP submission include whole-exome sequencing (WES) from four CDK4/6 inhibitor-naïve HR+/HER2- MBC PD cell lines (MGH10035.1, MGH10035.2, MGH358.1, and MGH358.2), their corresponding isogenic derivatives with acquired in vitro resistance to the CDK4/6 inhibitor palbociclib, and one PD cell line (MGH321.4) derived from a letrozole/ribociclib-resistant HR+/HER2- MBC tumor. MGH10035.1 and MGH10035.2 were derived from the same patient at different stages of treatment, as were MGH358.1 and MGH358.2.

Study phs004466

NCTN: EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, A Phase III Study (S0931)

Study ID: S0931 NCT Number: NCT01120249 SWOG Cancer Research Network Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, a Phase III Study (S0931) Trial Description: RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. PURPOSE: This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery. Clinical data presented in the following publication(s): PMID 37524096 Disease type(s): Kidney Neoplasm - Renal Cell Carcinoma Clinical Dataset(s) included: NCT01120249-D1 (PMID 37524096): There are two datasets for S0931's primary publication 37524096 (-D1 and -D2). The clinical dataset contains patient-level data (one row per patient), including eligibility, evaluability, treatment, demographic, baseline information, stratification factors, and unblinding. It also contains survival, cause of death, recurrence site, biopsy, and dose modification data. NCT01120249-D2 (PMID 37524096): There are two datasets for S0931's primary publication 37524096 (-D1 and -D2). This toxicity dataset contains event-level information (one row per patient per adverse event experience on trial). 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 phs004249

Targeting SS18-SSX Biology in Synovial Sarcomagenesis

This study investigates the biological consequences of BRD9 degradation in synovial sarcoma, a cancer driven by the SS18::SSX (SSX1 or SSX2) fusion oncoprotein. The study includes human synovial sarcoma cell lines, patient-derived xenograft (PDX) models. Molecular profiling was performed using RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin sequencing (ATAC-seq).The primary aim was to determine how depletion of the GBAF chromatin remodeling complex subunit BRD9 affects chromatin remodeling activity, transcriptional regulation, and tumor growth in synovial sarcoma. The study found that BRD9 degradation does not disrupt GBAF complex assembly but instead enhances chromatin remodeling activity, maintains or increases chromatin accessibility, and promotes expression of SS18::SSX target genes despite reduced chromatin occupancy. These findings provide a mechanistic explanation for the limited clinical efficacy of BRD9 degraders in synovial sarcoma.Data available through dbGaP will include raw and processed human genomic and epigenomic datasets generated from patient-derived tumors, including RNA-seq, ChIP-seq, ATAC-seq, together with associated experimental and clinical metadata necessary for data interpretation.

Study phs004771

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