8252 results for "canc*"

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• Collagen XVII Promotes Pancreatic Cancer Through Regulation of PIK3R5

  Pancreatic ductal adenocarcinoma (PDAC) contains a desmoplastic stroma that promotes the aggressive biology of this disease. While the varied mechanisms by which fibrillar collagens contribute to PDAC have been defined, little is known about the contribution of transmembrane collagens. Among this class of collagens, Collagen XVII uniquely contains an extensive intracellular domain that connects intracellular cytoplasmic components with the extracellular matrix. Collagen XVII is best characterized as the defining component of the type I hemidesmosome, an anchoring complex that attaches epithelial cells to the underlying basement membrane. In this study, we characterize the expression of collagen XVII in PDAC and the mechanisms by which it contributes to PDAC biology. We demonstrate that crosstalk between PDAC cells and cancer associated fibroblasts drive collagen XVII expression in vitro and xenograft tumor models in vivo. Genetic depletion of collagen XVII in low-passage patient derived cell lines diminishes their metastatic potential and ability to form tumors in mice. Whole transcriptome sequencing of tumors formed by cells with diminished collagen XVII levels revealed dramatically lower levels of PIK3R5, a regulatory subunit of class IB phosphatidylinositol-3-kinase (PI3K) that interacts with G protein-coupled receptors. Consistent with this, collagen XVII-deficient tumors exhibited lower levels of phosphorylated AKT, a downstream effector of PI3K. The studies highlight the importance of collagen XVII signaling in PDAC and define a novel mechanism by which collagen XVII mediates activation of PI3K.

  Study phs003641

• DAC for EGA study: Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer

  This is the Data Access Committee for the EGA study: Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer (temp ID 800).

  Dac EGAC50000000563

• Identifying genetic variants that alter TCR usage in the peripheral repertoire

  The relationship between genetic variation and CD8+ T-cell receptor (TCR) repertoire usage in patients receiving Immune Checkpoint Blockade (ICB) therapy for cancer is unexplored. We have conducted a genome-wide and human leukocyte antigen (HLA)-focused analysis of CD8+ T-cell TCR repertoire to identify genetic determinants of variable gene (V-gene) and CDR3 K-mer usage from samples taken prior to and after ICB (n=250). We identify 11 cis and 10 trans V-gene associations, primarily to the MHC, that meet genome-wide significance. TCR clones containing HLA associated V-genes were less stable across treatment, whilst at the single-cell level, genetically associated clones demonstrate subset enrichment and increased tumor reactivity expression profiles. Notably, patients with HLA-matched TCR clones demonstrate improved overall survival. Our work indicates a complex relationship between genotype and TCR repertoire in the context of ICB treatment, with novel implications for understanding factors relating to therapeutic response and patient outcomes.

  Study EGAS00001008189

• DAC for Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types

  While endometrioid and mucinous ovarian cancers represent nearly a quarter of ovarian cancers, their molecular characteristics and pathologic origins are poorly understood. To characterize the genomic and epigenomic alterations of these ovarian cancer subtypes and evaluate links to morphologically similar tumors from other sites, we performed sequence, copy number, mutation signature, rearrangement, and methylation analyses from tumor samples and matched normal tissues of 133 patients. These analyses included patients with ovarian endometrioid (n=44), ovarian mucinous (n=43), uterine endometrial (n=15), and gastrointestinal mucinous cancers (n=31). In addition to identifying genes previously known to be involved in these tumors, we identified alterations in RAD51C, NOTCH4, SMARCA1/4 and JAK1 in ovarian endometrioid, ESR1 in uterine endometrioid, and SMARCA4 in ovarian mucinous cancers. Whole genome sequencing revealed rearrangements involving PTEN, NF1, and NF2 in ovarian endometrioid tumors, and NF1 and MED1 in ovarian mucinous cancers. The number of alterations and affected genes in ovarian and uterine endometrioid cancers were similar as were genome-wide methylation profiles, suggesting that these tumors may have a similar tissue of origin. By contrast, methylation patterns in ovarian mucinous cancers were more similar to other gastrointestinal mucinous cancers, including mucinous cancers of the stomach, colon, and pancreas. These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers.

  Dac EGAC50000000341

• A Prospective Study of the Oral Microbiome and Pancreatic Cancer

  Two prospective cohort studies - the Black Women's Health Study and the Southern Community Cohort Study - were used to investigate the oral microbiome in relation to pancreatic cancer risk. Using a nested case-control study design, 148 cases and 510 matched controls were included (122 Black American pancreatic cancer cases and 409 matched controls). DNA was extracted from oral wash samples, using the PowerSoil Pro kit. Paired-end whole metagenomic shotgun sequencing was performed, using the Illumina HiSeq2000 platform with a read length of 100 bp (insert size 350 bp).

  Study phs002454

• Profiling Genome-Wide Circulating ncRNAs for the Early Detection of Lung Cancer

  Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Although imaging techniques such as low-dose computed tomography (LDCT), combined with tissue biopsies, have improved early detection rates, current diagnostic approaches are often limited by high false-positive rates, invasiveness, and radiation exposure, which lead to misdiagnosis and increased patient burden. Therefore, there is an urgent need for minimally invasive, accurate, and safe diagnostic biomarkers, particularly those derived from liquid biopsies such as blood-based exosomal RNA.This dataset specifically focuses on plasma-derived exosomal small non-coding RNAs (sncRNAs).A total of 233 de-identified plasma samples were obtained from Rush University Medical Center, including 116 NSCLC patients and 117 non-cancer controls. Exosomes were isolated from plasma, RNA was extracted, and small RNA sequencing was performed using the Illumina NextSeq 500 platform. Data available through dbGaP include individual-level raw sequencing files (FASTQ) and basic phenotype annotations of the plasma cohort.A diagnostic model was initially developed using small RNA-seq data from 1,446 tissue samples obtained from TCGA and GEO, identifying a robust sncRNA signature that distinguished NSCLC from non-cancer samples with an AUC of 0.90 in hold-out tissue validation. This signature was subsequently validated in the plasma exosome cohort, achieving an AUC of 0.84 in independent validation. The model demonstrated consistent diagnostic performance across subgroups stratified by age, sex, smoking history, cancer stage, and NSCLC subtype. Survival and functional analyses further supported the clinical and biological relevance of the identified sncRNAs. It is hoped that this resource will contribute to a better understanding of the sncRNA expression landscape in NSCLC and promote the development of non-invasive biomarkers for early cancer detection. These data may be applied to the investigation of transcriptomic and other risk factors, provide insight into cancer screening, tumor progression mechanisms, and prognosis prediction, and ultimately support precision medicine for NSCLC.

  Study phs004166

• A Translational, Pharmacodynamic and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer

  This phase IB clinical trial studied the pharmacodynamic changes induced by everolimus in patients with previously untreated, resectable non small cell lung cancer. Using a combination of in vivo and ex vivo assessments with FDG PET, immunohistochemistry and genomic assays, evidence of mTOR pathway perturbation was assessed in patients treated with everolimus, an allosteric mTOR inhibitor. Untreated patients served as controls for comparison. Key results from this work include a dose-dependent biologic effect of everolimus, signal of activity in RAS mutant tumors as well as near complete metabolic and pathologic response in a case of sarcomatoid lung cancer. These findings represent novel translational insights that can guide future development of mTOR inhibitors in lung cancer and other tumor types. Additionally, metabolic response and anatomic tumor shrinkage observed in a significant proportion of patients following a short of duration of therapy with everolimus suggests potential clinical utility of this agent in carefully-selected lung cancer patients.

  Study phs000829

• National Cancer Institute (NCI) Early Onset Malignancies Initiative (EOMI): Molecular profiling of Breast, Colon, Kidney, Liver, Multiple Myeloma, and Prostate among Racially and Ethnically Diverse Populations

  The Early Onset Malignancies Initiative (EOMI) is focused on collecting specimens from racially and ethnically diverse population groups with six different types of cancer (breast, prostate, colon, liver, kidney, and multiple myeloma). This initiative is a partnership between the Center for Research Strategy, the Center for Cancer Genomics and the Division of Cancer (DCP). DCP's NCI Community Oncology Research Program (NCORP) is a critical partner. The acquisition of the cancer and matching normal biospecimens in this initiative are from newly diagnosed early onset cancer patients who identify as Non-Hispanic Black, Hispanic, American Indian or Alaska Native, or Non-Hispanic White. The Minority/Underserved NCORPs sites will collect the samples for this project. By carrying out this initiative in the NCORP's national network of investigators, cancer care providers, and research institutions, the EOMI will harness the community-based partnerships to improve participation among these racial/ethnic groups. The NCORP investigators, as participants in NCI's clinical trials network, will annotate the biologic samples with clinical information that will enhance the ability to answer questions about molecular determinants of early disease, treatment response, and/or prognosis. The EOMI will be a step forward in addressing racial/ethnic disparities and in understanding cancer in underserved populations.

  Study phs001952

• UCL Translation Uro-Oncology Data Access Committee will govern access to data generated from the Translation Uro-Oncology groups of the UCL Cancer Institute and UCL Division of Surgery & Interventional Science

  Dac EGAC00001000471

• Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration

  The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. We used continuous long-read sequencing of oropharyngeal cancers and cervical cancer cell lines to resolve structural variation induced by HPV. We discovered a previously undescribed form of structural variation, "heterocateny," characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer.

  Study phs003396

• The Haplotype-Resolved Genome and Epigenome of the Aneuploid HeLa Cancer Cell Line

  The genomic architecture of HeLa remains largely unexplored beyond its karyotype, partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing of the HeLa CCL-2 strain, examined point- and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for HeLa S3 and eight additional strains. We find that HeLa is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with RNA-seq and ENCODE Project data sets to phase the HeLa epigenome. This revealed strong, haplotype specific activation of the proto-oncogene MYC by the integrated HPV-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes. Reprinted from Adey et. al. 2013, Nature, with permission from Nature Publishing Group.

  Study phs000642

• DNA Repair Capacity for Lung Disease Risk Assessment

  A focus of this work was to address the extent to which susceptibility for lung cancer varies by gene-environment-phenotype interactions involving DNA repair capacity and differences in risk from environmental stressors. GWAS from a subset of subjects from the Lovelace Smokers Cohort and New Mexico Lung Cancer cohort were used to derive polygenic risk scores for DNA repair pathways (nucleotide excision, base excision, single strand break, non-homologous, homologous recombination). Logistic regression analysis was used to examine the association between polygenic risk score and lung cancer status. Polygenic risk scores were grouped by quartiles. Only diminished base excision repair was associated with increased risk for lung cancer at the 25-50% quartile and approached significance at the 50-75% quartile.

  Study phs004063

• APOBEC Mutagenesis, Kataegis, Chromothripsis in EGFR-Mutant Osimertinib-Resistant Lung Adenocarcinomas

  Expanding on studies investigating apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) mutagenesis in histological transformation of epidermal growth factor receptor (EGFR)-mutant lung cancers, it has been hypothesized that mutational signature analysis may help better understand acquired resistance to targeted therapies. Using mutational signature analysis in Receptor Tyrosine Kinase (RTK) driven lung adenocarcinomas, more specifically EGFR mutant lung cancer, APOBEC dominant mutational signatures were noted more frequently in subclonal post Tyrosine Kinase Inhibitor (TKI) treatment biospecimen samples and in the presence of large-scale genomic rearrangements. This is hypothesized to be due to the pressure of treatment with TKIs; a fact that should be further explored and can be potentially manipulated in order to overcome drug resistance.

  Study phs003812

• HeLa Cell Genome Sequencing Studies

  HeLa is a human epithelial adenocarcinoma cell line that was derived from biopsy specimens of a 31-year old patient named Henrietta Lacks who was being treated for cervical cancer at The Johns Hopkins University Hospital in 1951. The specimens were obtained without her knowledge or consent just before her death in 1951. HeLa is the oldest and most widely used human cell line and has been an extraordinarily important resource for researchers throughout the world. HeLa cells have served as a standard for understanding many fundamental biological processes, such as testing the polio vaccine, establishing basic techniques for cloning and in vitro fertilization, identifying the cause of cervical cancer (HPV), and advancing the development of anti-cancer drugs.This study contains all authorized whole genome sequence data of the HeLa cell line from datasets currently in dbGaP. These data have been approved for health, medical, and/or biomedical research purposes. Access to these data can be granted for one year. Accessible data will include the studies listed on this page and any additional authorized datasets that become available during this one-year period. The HeLa Genome Data Access Working Group of the Advisory Committee to the Director (ACD) will review requests from the research community for access to these datasets and assess whether the requests align with the terms of use defined in the HeLa Genome Data Use Agreement. The Working Group's findings will be reported to the ACD, and the ACD will make recommendations to the NIH Director about whether a request should be approved or disapproved. The NIH Director will decide whether access to the data will be granted.

  Study phs000640

• Tumor-associated neutrophil 1 precursors impair homologous DNA repair and promote sensitivity to PARP-inhibition

  Tumor evolution is one of the major mechanisms responsible for acquiring therapy resistant and more aggressive cancer clones. Whether the tumor microenvironment through immune-mediated mechanisms might promote the development of more aggressive cancer types is crucial for the identification of additional therapeutical opportunities. Here, we identify a subset of tumor-associated neutrophils, defined as tumor-associated neutrophil precursors (PreNeu). These PreNeu are enriched in highly proliferative hormone-dependent breast cancers and impair DNA repair capacity

  Study EGAS00001008154

• WES data of pediatric cancer patients with P/LP variants in HBOC-related genes

  The current study aimed to identify (likely) pathogenic germline variants(LP/PVs) in 25 adult-onset HBOC-related genes within a cohort of 372 pediatric cancer patients. For this purpose we performed (paired-end) whole exome sequencing (WES) using Ilumina sequencing technology. The files uploaded here belong to the 27 individuals with such a LP/PV. The project provides insight into the prevalence and spectrum of such variants in childhood cancer, contributing to the understanding of genetic predisposition in pediatric oncology.

  Dataset EGAD50000001561

• University of Sydney Thyroid Cancer Data Access Committee

  This Data Access Committee (DAC) manages access to genomic data generated by the Thyroid Cancer Research Group at the University of Sydney and Royal North Shore Hospital. The DAC will evaluate data access requests to ensure they align with participant consent and the conditions approved by the Northern Sydney Local Health District Human Research Ethics Committee. Requests will be reviewed for scientific validity, alignment with the original consent, and compliance with institutional and regulatory data governance policies.

  Dac EGAC50000000661

• Data access committee for "Detection of brain cancer using genome-wide cell-free DNA fragmentomes"

  The data access committee for “ Detection of brain cancer using genome-wide cell-free DNA fragmentomes”. The DAC is comprised of Drs. Dimitrios Mathios, Jillian Phallen, Victor Velculescu, Robert Scharpf, Noushin Niknafs, and Shashikant Koul, and can be contacted at skoul3@jh.edu.

  Dac EGAC50000000605

• Single Cell RNA-Sequencing of BCG Naive and Recurrent Non-Muscle Invasive Bladder Cancer Reveals a CD6/ALCAM-Mediated Immune-Suppressive Pathway

  Non-muscle invasive bladder cancer (NMIBC) represents 70–80% patients with newly diagnosed bladder cancer, and Bacillus Calmette-Guerin (BCG) remains a cornerstone treatment for intermediate- and high-risk NMIBC to prevent disease recurrence and progression. However, a significant number of patients experience recurrence after their first course of BCG, posing significant challenges in the management of the disease. We conducted single cell RNA sequencing (scRNA-Seq) on freshly collected NMIBC samples, distinguishing between those naive to BCG treatment and those that recurred post-BCG treatment. We observed a clear activation of inflammatory pathways across cell types during recurrence, but these were not associated with canonical immune checkpoint or T cell exhaustion phenotypes. Analysis of cell-to-cell communication revealed enhanced interactions between T cells and urothelial cells in BCG-recurrence, predominantly modulated by CD6 and activated leukocyte cell adhesion molecule (ALCAM). Furthermore, we found CD6hi T cells to be immunosuppressed and enriched in recurrent samples, suggesting a potential role for CD6 as an immune evasion signal in NMIBC.

  Study phs003742

• The Formation and Propagation of Human Robertsonian Chromosomes

  Robertsonian chromosomes are a type of variant chromosome found commonly in nature. Present in one in 800 humans, these chromosomes can underlie infertility, trisomies, and increased cancer incidence. Recognized cytogenetically for more than a century, their origins have remained mysterious. Recent advances in genomics have allowed us to assemble three human Robertsonian chromosomes completely. We identify a common breakpoint and epigenetic changes in centromeres that provide insight into the formation and propagation of common Robertsonian translocations. Further investigation of the assembled genomes of chimpanzee and bonobo highlights the structural features of the human genome that uniquely enable the specific crossover event that creates these chromosomes. Resolving the structure and epigenetic features of human Robertsonian chromosomes at a molecular level will pave the way to understanding how chromosomal structural variation occurs more generally, and how chromosomes evolve.

  Study phs003920

• 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

• Data Access Committee for Translational analyses from a phase II study of pembrolizumab and epigenetic modification with azacitidine in platinum-resistant epithelial ovarian cancer

  This DAC is responsible for request review and handling related to the study above.

  Dac EGAC50000000697

• Data Access Committee for Triple Negative Breast Cancer dataset

  Dac EGAC00001003584

• DAC for "Establishment and characterization of circulating tumor cells-derived organoids from metastatic breast cancer patients."

  Dac EGAC00001003514

• WGS of Five Pancreatic Cancer Patients-Tumor and Normal

  We performed whole genome sequence on tumor-derived and normal cell lines from patients who had terminal pancreatic cancer and consented for rapid autopsy upon their death. The 5 samples are from Dr. Christine Iacobuzio-Donahue's rapid autopsy program as reported in Boland et al. (PLOSOne, 2024, In Press, PMID 38352348).

  Study phs003775