6048 results for "canc*"

in 47.24 milliseconds.

• The Cancer Dependency Map (DepMap)

  The Cancer Dependency Map (DepMap) aims to accelerate precision cancer medicine by creating a comprehensive map of tumor vulnerabilities. The DepMap project genomically profiles a wide range of cancer models and characterizes them for their sensitivity to genetic and compound perturbations. The data is computationally analyzed to create a systematic overview of the genetic dependencies and compound sensitivities of cancer types and the predictive biomarkers that point to patient populations most likely to benefit from targeting of these vulnerabilities. The DepMap public portal has become a comprehensive resource to identify cancer vulnerabilities by providing datasets at scale, cutting-edge computational tools, and sophisticated visualization tools that together have accelerated the discovery of novel targets and biomarkers. Please visit Depmap.org to access the public portal.

  Study phs003444

• KDM6A Loss Triggers an Epigenetic Switch that Disrupts Urothelial Identity and Drives Cell Proliferation in Bladder Cancer

  Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. How mutations of this chromatin modifier impact the epigenetic landscape to promote carcinogenesis is poorly understood. Here, we demonstrate that KDM6A loss triggers an epigenomic switch that disrupts urothelial identity and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 binds KDM6A at enhancers to activate genes instructing urothelial differentiation. In KDM6A-deficient cells, we observed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn represses FOXA1 target genes and activates cell-cycle progression genes. Importantly, ATF3 depletion reverses the cell proliferation phenotype. These data establish that KDM6A loss creates an epigenetic state that drives tumor growth in an ATF3-dependent manner, forging a molecular vulnerability that can be targeted by novel therapeutic strategies.

  Study phs002801

• Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis

  We recruited cases of Langerhans cell histiocytosis (LCH) who were recruited to the Children's Oncology Group Childhood Cancer Research Network, Project:EveryChild projects, or to a local patient biobank to conduct an expanded genome-wide association study for risk variants and to perform post-GWAS analysis of a previous hit in the SMAD6 gene. Publicly available control data were used for our analyses; however, here we provide the SNP array data and targeted SMAD6 sequence data for the LCH cases and some non-LCH cases included in the analysis.

  Study phs004547

• MP2PRT: Evaluation of an Inflammation Polygenic Risk Score (iPRS) to Predict Cancer Related Cognitive Impairment and Fatigue in Patients Receiving Chemotherapy for Non-Metastatic Breast Cancer in URCC0701 and URCC10055

  This study is a secondary analysis of cancer related cognitive impairment (CRCI) and cancer related fatigue (CRF) among participants in URCC0701 and URCC10055 from the University of Rochester NCI Community Oncology Research Program (NCORP) Research Base. CRCI and CRF are common, troublesome, and dose-limiting toxicities reported by patients undergoing breast cancer chemotherapy that have an etiologic basis linked to low-grade systemic inflammation. Chronic, low-grade systemic inflammation is, in part, genetically determined with common single nucleotide polymorphisms (SNPs) capturing variation across individuals. This study aimed to 1) determine whether an inflammation polygenic risk score (iPRS) is associated with CRCI or CRF, 2) determine whether the relationship between the iPRS and CRCI or CRF is modified by exercise at the time of cancer treatment, 3) identify SNPs associated with serum cytokines measured at the time of cancer treatment, and 4) identify novel CRCI- and CRF-associated risk SNPs via genome-wide association analyses. We found that there was a significant inverse correlation between the iPRS and change in fatigue score from pre-chemotherapy to post-chemotherapy while there was no statistically significant association between the iPRS and cognitive impairment score. The inverse relationship between the iPRS and fatigue may be explained in part by the finding that the iPRS was also significantly associated with greater pre-chemotherapy fatigue, suggesting that women with a genetic predisposition to low-grade systemic inflammation (i.e., high iPRS) have more fatigue at the time of breast cancer diagnosis and, therefore, are less likely to worsen over the course of treatment. In contrast, women with a low iPRS had significantly less fatigue pre-chemotherapy and a significant worsening of fatigue from pre- to post-chemotherapy. The relationship between the iPRS and fatigue remained after adjustment for patient and cancer treatment covariates and was most pronounced in women who reported regularly exercising for at least 6 months prior to starting their cancer treatment. Exploratory genome-wide analysis identified a novel risk locus on chromosome chr6q27, tagged by rs9365961, associated with CRCI. This locus is upstream of TBXT, which encodes an embryonic nuclear transcription factor previously associated with susceptibility to neural tube defects. The genome-wide SNP data, patient-reported CRCI and CRF outcome measures, and covariate data used in this analysis are available through dbGaP.

  Study phs003688

• Metabolic Biomarkers in Thoracic Cancers

  Here we present RNA sequencing (RNA-Seq) of non-small cell lung cancer (NSCLC) and adjacent lung tissue. These samples were acquired from primarily untreated, surgically resected primary tumors. The first analysis published with this data was to determine the metabolic signatures between primary tumors and adjacent lung tissue.The associated clinical trial (NCT02095808) includes patients with many kinds of thoracic cancers, including NSCLC and other diseases, such as thymoma and esophageal adenocarcinoma. However, the current dbGaP data is focused on the NSCLCs described in the associated paper.

  Study phs003880

• 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

• Childhood Cancer Data Initiative (CCDI): A Cohort of Hispanic Children with Acute Lymphoblastic Leukemia; Bloom Syndrome in a Mexican American Family with Rhabdomyosarcoma

  Retrospective case-control genetic study of Hispanic children with acute lymphoblastic leukemia (ALL) treated 1994-2013, comparing 14 treatment-related pancreatitis (TRP) cases to 46 treatment-matched controls without pancreatitis. Targeted sequencing of 23 genes (pancreatitis-related and asparagine-metabolism genes) was performed from post-remission blood DNA; select HLA types were inferred from whole-exome data in cases. CFTR and ASNS variants were enriched in TRP (notably CFTR V470M, OR 4.27, p=0.025).

  Study phs002823

• 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

• Childhood Cancer Data Initiative (CCDI): Metastatic Osteosarcoma snMultiome Profiling

  Metastatic osteosarcoma is an aggressive bone malignancy affecting pediatric, adolescent, and young adults. While recent research has increasingly focused on understanding the complex biology of the osteosarcoma microenvironment, the tumor vasculature is understudied, especially in the context of metastatic disease. To address this, we performed single-nuclei multi-ome (RNA+ATAC) sequencing on a cohort of 24 human metastatic osteosarcoma specimens. Our data shows that endothelial cells universally exhibit a hybrid endothelial–mesenchymal state consistent with endothelial-to-mesenchymal transition (EndMT). Additionally, we uncovered that a subset of diploid endothelial cells adopts an osteoblastic cell fate as evidenced by gene expression and gene regulatory network (GRN) analysis. Joint copy-number analysis of our dataset identified a subset of osteosarcoma cells with endothelial transcriptional programs and GRNs, indicative of vascular mimicry. In vitro assays and in vivo lineage tracing experiments using syngeneic murine models validated both vascular mimicry and endothelial to-osteoblastic transdifferentiation. Collectively, these findings highlight the remarkable plasticity and lineage infidelity of both endothelial and osteosarcoma cells in patient specimens and a metastatic syngeneic murine model, provide novel insights into the functional role of endothelial cells in the metastatic osteosarcoma microenvironment, and challenge current understanding of osteosarcoma biology.

  Study phs004490

• Childhood Cancer Data Initiative (CCDI): Frameshift Mutation Profiling of Constitutional Mismatch Repair Deficiency Syndrome Patients

  Samples from patients with Constitutional Mismatch Repair Deficiency Syndrome (CMMRD) were sequenced using the Archer NextSeq platform to detect frameshift mutations in cell-free DNA (cfDNA), matched tumor samples, and other tissue types. The goal of the study is to evaluate whether a frameshift mutation biomarker panel can be used for disease monitoring. Limited treatment information is included when available. The listed genes represent those in which recurrent frameshift mutations were identified and evaluated as candidate biomarkers for disease monitoring in CMMRD.

  Study phs004017