6048 results for "canc*"

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• An Ultrasensitive Method for Detection of Cell-Free RNA

  Our study describes the development of a novel method for cell free RNA (cfRNA) analysis called RARE-Seq (Random priming & Affinity capture of cell-free RNA fragments for Enrichment analysis by Sequencing). We find RARE-Seq improves the limit of detection for tumor-naïve cancer detection while maintaining high specificity. We explore the potential utility of RARE-Seq in diverse clinical applications, including non-invasive ctRNA genotyping, treatment resistance monitoring, and molecular characterization of non-malignant conditions.

  Study phs004091

• Interdisciplinary Approaches for Understanding how Arsenic and Micronutrients Affect the Epigenome to Influence Spina Bifida Risk

  This hospital-based case-control study was conducted in Bangladesh between December 2016 and December 2022 to investigate the association between environmental arsenic exposure and the risk of spina bifida. The study enrolled children with spina bifida (cases) and unaffected children (controls), along with their biological parents. Cases included infants under one year of age with clinically confirmed diagnoses of myelomeningocele or meningocele at the National Institute of Neurosciences & Hospital (NINS). Controls were frequency-matched on age and recruited from the same catchment area through NINS and Dhaka Shishu Hospital. Children with conditions potentially related to arsenic exposure, such as keratosis or cancer, were excluded from the control group. A small subset of case families were reclassified as controls following surgical reevaluation and a revised diagnosis of lipomeningocele, then later removed from the control group. They are no longer assigned to either the case or control category in the datasets. Saliva samples were collected from children and parents using Oragene® kits and stored at room temperature before shipment to Boston, MA, USA. DNA extraction was carried out with the Maxwell® RSC Buccal Swab DNA kit. A total of 749 saliva DNA samples, representing 713 unique individuals and 36 replicates, were shipped to the Broad Institute for analysis. Samples were randomized across Illumina Global Screening Array (GSA) chips to minimize batch effects. The primary molecular technology employed in this study was the Illumina Global Screening Array (GSAMD-24v1-0), which includes approximately 688,000 genetic markers. Data generated include raw and processed genotype files as well as a comprehensive quality control report. The genotyping dataset available through dbGaP will consist of genotype calls from spina bifida cases, controls, and their parents, along with associated demographic, clinical, and exposure metadata, enabling future analyses of gene-environment interactions in the context of neural tube defect risk.

  Study phs003733

• Real-Time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

  Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole exome sequencing (WES) and RNA-sequencing (RNA-Seq) for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data. Twenty-six patients had germline and/or somatic alterations in DNA-damage repair genes, and 5 additional patients had mutational signatures of homologous recombination deficiency but no identified causal genomic alteration. Two patients had oncogenic in-frame BRAF deletions, and we report the first clinical evidence that this alteration confers sensitivity to MAP-kinase pathway inhibition. Moreover, we identified tumor/stroma gene expression signatures with clinical relevance. Collectively, these data demonstrate the feasibility and value of real-time genomic characterization of advanced PDAC.

  Study phs001652

• 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

• scRNA-seq of Multiple Myeloma and Tumor Microenvironment Cells from Bone Marrow During CAR T-Cell Therapy

  Multiple myeloma (MM) is a treatable, yet incurable, plasma cell malignancy for which molecular mechanisms driving the development of therapy resistance remain largely elusive. To better characterize tumor intrinsic and immune tumor microenvironment (iTME) factors associated with CAR T-cell efficacy, scRNAseq (10x Genomics V3.1) was performed on purified MM cells (CD138+) and associated iTME cells (CD138- mononuclear cells) from fresh bone marrow aspirates harvested prior to therapy in 13 patients treated at Moffitt Cancer Center. After biopsy, 7 of these patients were treated with ABECMA (idecabtagene vicleucel or ide-cel) and 6 were treated with ciltacabtagene autoleucel (cilta-cel or CARVYKTI®). Bone marrow biopsies were collected between 2021 and 2023. In addition to the molecular data, demographic information for the samples is provided. These data allow for the assessment of transcriptional signatures at the single-cell level in both the tumor and its bone marrow iTME, associated with CAR T-cell therapy in MM patients.

  Study phs004878

• Genome Sequencing of Individuals with PTEN Hamartoma Tumor Syndrome

  This study investigated genomic modifiers of cancer and neurodevelopmental outcomes among individuals with PTEN hamartoma tumor syndrome (PHTS), a rare hereditary disorder caused by germline PTEN variants and associated with broad clinical variability, including cancer predisposition, autism spectrum disorder, developmental delay, and intellectual disability. The primary aim was to determine whether additional inherited genomic variation beyond PTEN contributes to divergent clinical manifestations, particularly the development of cancer versus neurodevelopmental disorders.The main analytic cohort consisted of 543 probands with germline PTEN variants, including participants with cancer, neurodevelopmental disorders, both cancer and neurodevelopmental disorders, or neither phenotype at the time of consent.Molecular data were generated from germline DNA extracted from peripheral blood leukocytes using PCR-free whole-genome sequencing at approximately 30× coverage. Sequence reads were aligned to the hg38 human reference genome, followed by standard variant calling, quality control, annotation, and downstream genomic analyses. The study evaluated pathogenic or likely pathogenic variants in established cancer predisposition genes and neurodevelopmental disorder genes, and also performed genome-wide common-variant and rare-variant association analyses to identify candidate modifier loci.Principal findings showed that a subset of individuals with PHTS carried additional germline variants in known cancer- or neurodevelopment-related genes. Specifically, additional cancer-associated variants were identified in 37 of 543 probands, most commonly involving MITF, DICER1, and BRCA2, while neurodevelopment-associated variants were identified in 43 of 543 probands, including variants in DHCR7, POLG, ARSA, and other genes. Genome-wide analyses further identified candidate modifier loci with potential biological relevance to PTEN signaling and phenotype divergence, including ZNF713, TPTE2P1, and PDPK1. These findings support the hypothesis that PHTS clinical outcomes are influenced not only by germline PTEN variation, but also by additional inherited genomic modifiers.Data to be made available through dbGaP will include de-identified individual-level germline whole-genome sequencing data and associated phenotype information relevant to PHTS, cancer status, neurodevelopmental status, demographic variables, and PTEN variant classification, consistent with participant consent and institutional certification. The individual-level data are intended for controlled access.

  Study phs004787

• A Personalized Neoantigen Vaccine Generates Anti-Tumor Immunity in High-Risk Renal Cell Carcinoma

  Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumor, and result in clinical activity are largely unknown, particularly in patients with lower mutation burden tumors. We conducted a phase I trial testing a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV), with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 months from surgery, none of the 9 initial participants experienced a recurrence of RCC. No dose-limiting toxicities were observed. All patients generated T cell immune responses against PCV antigens, including RCC driver mutations in VHL, PBRM1, BAP1, KDM5C, and PIK3CA. Following vaccination, there was a durable expansion of peripheral T cell clones, and T cell reactivity against autologous tumor was detected in 7 of the 9 patients. Our results demonstrate that neoantigen-targeting PCVs in high-risk RCC are highly immunogenic, capable of targeting key driver mutations, and induce anti-tumor immunity. These observations, in conjunction with the absence of recurrence in all 9 vaccinated patients, highlights the promise of PCV as effective adjuvant therapy in RCC. We are submitting whole exome sequencing (WES) data from whole blood samples and tumor FFPE samples, and RNA-Seq data from tumor FFPE samples. We are also submitting RNA-Seq data from purified tumor samples. Single-cell RNA sequencing (scRNA-seq) data will be submitted for skin samples (vaccine site biopsies at weeks 0, 4, and 13), tumor samples (including resected metastatic tumor samples for two patients), and normal kidney samples. Bulk T-cell receptor sequencing (TCR-seq) data will be submitted for blood samples.

  Study phs003710

• Single-Cell RNA-Sequencing of Human Prostatectomy Tissue

  The tissue microenvironment in prostate cancer is profoundly altered. How prostate cancer cells and their precursors mediate those changes is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we performed extensive single-cell RNA-sequencing (scRNA-seq) to assess the transcriptional profiles of the tissue microenvironment in prostate tissues from prostatectomies from men diagnosed with prostate cancer. For each subject, benign-enriched and tumor-enriched tissues were collected from the peripheral zone of the prostate. Additionally, to understand zone-specific differences of the prostate, benign tissues were also collected from the transition and central zones.

  Study phs003480

• Genomic Alterations and Transcriptional Phenotypes in Circulating Tumor DNA and Matched Metastatic Tumor

  We analyzed a prospective cohort of 49 plasma samples obtained before, during, and after treatment from 20 patients with recurrent small cell lung cancer. We conducted cfDNA low-pass whole genome sequencing (0.1X coverage) and exome sequencing (130X coverage) in comparison with time-point matched tumor characterized using whole-exome (130X) and transcriptome sequencing. A direct comparison of cfDNA and tumor biopsy revealed that cfDNA not only mirrors the mutation and copy number landscape of the corresponding tumor, but also identifies clinically relevant resistance mechanisms and cancer driver alterations not detected in matched tumor biopsies. Longitudinal cfDNA analysis reliably tracks tumor response, progression, and clonal evolution. Sequencing coverage of plasma DNA fragments around transcription start sites showed distinct treatment-related changes and captured the expression of key transcription factors n the corresponding SCLC tumors.

  Study phs003689

• Women's Health Initiative (WHI) - Life and Longevity After Cancer (LILAC) (WHI-LILAC-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: The LILAC substudy was initiated to collect information on cancer treatment and long-term outcomes in women diagnosed with eight selected cancers during their participation in WHI.Background: Improvements in early detection and treatment have led to a surge in the number of cancer survivors in the United States creating a demand for a better understanding of their health concerns. Cancer survivor health concerns are diverse and complex due to the heterogeneity among individuals, cancer type, and treatment variability. To effectively examine these concerns, new resources need to be developed, including a much more comprehensive assessment on a large sample with longer-term follow-up than is typically available in cancer clinical trials. The WHI cohort, which is a large study with long-term follow-up, continues to be a good resource to study issues related to aging and health. The LILAC substudy was initiated with WHI participants who had been diagnosed with cancer to examine cancer survivorship among older women.Participants: Participants with no cancer (other than non-melanoma skin cancer) prior to enrollment in WHI and a confirmed invasive cancer diagnosis during WHI follow-up of one of the eight selected cancers were eligible for LILAC.A total of 9934 WHI participants living with cancer were eligible. Of those, 7751 consented and returned the baseline survey. This included 821 participants with melanoma, 781 participants with colorectal cancer, 648 participants with endometrial cancer, 397 participants with lung cancer, 4173 participants with breast cancer, 442 participants with non-Hodgkin lymphoma, 181 participants with leukemia, and 208 participants with EOC (which includes ovarian, fallopian tube and primary peritoneal cancers). Design: Participants still in active WHI follow-up who were eligible for the LILAC substudy were sent an invitational mailing that included a baseline survey. Baseline surveys collected data on initial cancer treatment, symptoms after treatment completion, and quality of life. WHI participants who consented to the LILAC substudy were subsequently sent annual surveys. Annual surveys collected any updates on treatment, as well as other topics related to cancer survivorship such as social support. Additional treatment information was obtained from Medicare claims and medical records.Conclusions: The LILAC substudy provides a resource for studying cancer survivorship among older women diagnosed with eight selected cancers.

  Study phs004174