12310 results for "cancer rna-seq"

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• Bone marrow single cell genomics from blood cancer samples

  Four different types of transcriptomic single-cell sequencing of blood from childhood B acute lymphoblastic leukemia.

  Dataset EGAD00001011055

• Circulating Cell-free DNA Whole Genome Sequencing from Head and Neck Cancer Patients

  This dataset contains plasma-derived circulating cell-free DNA (cfDNA) whole genome sequencing (WGS) data from patients diagnosed with head and neck squamous cell carcinoma. cfDNA was extracted from plasma collected at defined clinical timepoints.

  Dataset EGAD50000001828

• RNA Expression in Diverse Donor Derived Dermal Fibroblasts Correlates with Reprogramming to Pluripotency

  The cohort used in this study includes 36 African American (17 female, 19 male) and 36 White American (19 female, 17 male) individuals. The total cohort has a median age of 32 years, with a range of 20-64 years. The African American cohort has a median age of 34, with a range of 21-52 years. The White American cohort has a median age of 31, with a range of 20-64 years. Primary dermal fibroblast lines were derived from skin biopsies obtained from adult individuals at the NIEHS under institutional review board approved protocol human subjects 10-E-0063, "Sample Collection Registry for Quality Control of Biological and Environmental Specimens and Assay Development and Testing protocol" (ClinicalTrials.gov #NCT01087307). All participants gave written informed consent for tissue donation. Donor sex, age, and ancestry were voluntarily self-reported. Fibroblast cells were reprogrammed via lentiviral transduction using six transcription factors contained in three plasmids (ADDGENE/PSIN4-EF2-N2L, ADDGENE/PSIN4-EF2-O2S and ADDGENE/PSIN4-CMV-K2M). Reprogramming efficiency was determined by alkaline phosphatase staining of triplicate 10cm reprogrammed dishes containing colonies, which were then scanned. The saved images were analyzed with ImageJ 1.51h (Wayne Rasband, National Institutes of Health, USA) to count colonies, using color threshold adjusted and binary converted images of each dish. Triplicate plates were averaged and reported as colony counts or percent reprogramming efficiency ((# of colonies/250,000) x100). The African American cohort had reprogramming efficiencies ranging from 0.06-1.37%, with a median of 0.655%. The White American cohort had reprogramming efficiencies ranging from 0.02-1.13%, with a median of 0.455%. Our goal was to define transcriptomic heterogeneity that could be contributing to differences in reprogramming efficiency between individuals and between groups. Total RNA was obtained from dermal fibroblasts and matched iPSCs. For each sample, 500 ng total RNA was used as input for preparation of whole transcriptome rRNA depleted libraries. An adapter-ligated library was prepared with the KAPA HyperPrep Kit (KAPA Biosystems, Wilmington, MA) using Bioo Scientific NEXTflex™ DNA Barcoded Adapters (Bioo Scientific, Austin, TX, USA) according to KAPA-provided protocol. Sequencing was performed using an Illumina HiSeq 2500 following Illumina-provided protocols for 2x150 bp paired-end sequencing. Each transcriptome was sequenced to a target depth of 125 million reads. The following mean raw reads were obtained: African American dermal fibroblasts= 129,571,450; White American dermal fibroblasts= 131,939,505; African American iPSCs= 132,501,335; White American iPSCs= 134,394,164. Raw reads were aligned to hg19 using the STAR alignment tool (https://github.com/alexdobin/STAR). The following mean aligned reads were obtained: African American dermal fibroblasts= 123,315,343; White American dermal fibroblasts= 125,178,035; African American iPSCs= 123,148,312; White American iPSCs= 123,886,992. Reprinted from L. C. Mackey et al., Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming. Stem Cells 36, 1697-1708 (2018), with permission from Wiley. Reprinted from L. S. Bisogno et al., Ancestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological processes. Science Advances 6 (47) (2020) (PMID: 33219026), with permission from AAAS.

  Study phs002341

• Pathways Study

  The Pathways Study (NCI R01 CA105274, PI: Kushi), is a prospective cohort study of a diverse population of recently diagnosed breast cancer survivors in KPNC. The aims are to examine the effect on recurrence and survival of 1) lifestyle factors such as diet, physical activity, and use of complementary and alternative therapies and 2) molecular factors such as biomarkers of inflammation and tumor DNA methylation profiles. Recruitment into the cohort was from January 2006 to May 2013. Baseline data collection was by in-person interview (on average two months post-diagnosis), with follow-up via mailed or phone questionnaires at 6, 24, and 72 months and outcomes and comorbidities at 12, 24, 48, 72, and 96 months post-enrollment. The Pathways Study is now funded through May 2021 as a cancer cohort infrastructure grant (U01 CA195565, MPI: Kushi/Ambrosone). The Pathways baseline interview consists of interviewer- and self-administered questionnaires. Interviewer-administered questionnaires collected information including demographics, family health history, pregnancy health history, menstrual history, history of breast care screening procedures, smoking history, hormone use, medication history, and vitamin and mineral use. Self-administered questionnaires collected information on diet, physical activity, CAM use, lymphedema, and psychosocial and quality of life measures.

  Study phs001534

• Transcriptome sequencing of human colon organoid after co-cultivation with Bifidobacterium longum

  The large intestine has a dense milieu of indigenous bacteria, generating a complex ecosystem with crosstalk between individual bacteria and host cells. In vitro host cell modeling and bacterial interactions at the anaerobic interphase have elucidated the crosstalk molecular basis. Although classical cell lines derived from patients with colorectal cancer including Caco-2 cells are used, whether they adequately mimic normal colonic epithelial physiology is unclear. To address this, we performed transcriptome profiling of Caco-2 and Monolayer cells derived from healthy Human Colonic Organoid (MHCO) cultured hemi-anaerobically. Coculture with the anaerobic gut bacteria, Bifidobacterium longum subsp. longum differentiated the probiotic effects of test cells from those of physiologically normal intestinal and colorectal cancer cells. We cataloged non- or overlapping gene signatures where gene profiles of Caco-2 cells represented absorptive cells in the small intestinal epithelium, and MHCO cells showed complete colonic epithelium signature, including stem/progenitor, goblet, and enteroendocrine cells colonocytes. Characteristic gene expression changes related to lipid metabolism, inflammation, and cell-cell adhesion were observed in cocultured live Bifidobacterium longum and Caco-2 or MHCO cells. B. longum-stimulated MHCO cells exhibited barrier-enhancing characteristics, as demonstrated in clinical trials. Our data represent a valuable resource for understanding gut microbe and host cell communication.

  Study JGAS000740

• Development of New Diagnostics, Therapeutics, and Prevention Methods for Personalized Medicine Based on Comprehensive Cancer-Related Gene Exome Analysis and Information Analysis Using Cancer Specimens Stored in TMDU Biobank.

  Biobanked tumor samples are a valuable resource in real-world solid tumor research. Panel-based genomic profiling enables the identification of clinically significant alterations that inform personalized diagnostic and treatment decisions. This study aimed to characterize the genomic landscape of solid tumors collected through the TMDU Biobank by summarizing mutational, copy number, and gene fusion alterations in a large and diverse patient cohort. This dataset contains summary-level genomic information from 1,996 tumor samples analyzed by ACT Genomics and ACT med using the ACTOnco Comprehensive 440-Gene Cancer Panel. Data provided includes (1) gene-level mutation counts, (2) a summary of copy number alterations, and (3) a summary of detected fusion events. Clinical attributes such as ICD-10 codes, age group, sex, tumor mutational burden (TMB), and microsatellite instability (MSI) status were included at the aggregate level. Summary statistics were generated from three source tables (gene, sample, and copy number data) using standardized processing rules. Due to contractual and ethical considerations, individual-level mutation locations and raw sequence data are not included; only summary-level information is provided. This dataset will support future research in tumor-type-specific genomic patterns, molecular characterization of solid malignancies, and precision oncology.

  Study JGAS000863

• The last addition to the list of clonal evolution studies in the EGA

  Tumours of different types may arise from a single cell with at least one malignant mutation. Accumulation of subsequent hits generates lineages of cells with different cancer transformation power; thus, every clone follows an autonomous evolution, and several clones may co-exist into the same solid or liquid tumour. Clonal evolution studies are not new: the conceptual power of this approach has been recognized since the early ’80, especially in leukaemia patients. Nonetheless, these studies greatly benefit from recent technological improvements -machineries and protocols-, which enable ever-increasing sequencing depth, allowing the detection of low frequency variants and consequently more tumour clones. Note: the figure belongs to the original paper and is owned by the authors. Researchers at the University of Kyoto in Japan, have indeed used state of the art knowledge to investigate the clonal evolution of chronic myeloid leukemia (CML) in a large panel of patients. CML progresses from a majoritarian benign chronic phase into an often fatal blast crisis phase. It is nowadays known that blast crisis are triggered by genetic instability and disrupted DNA repair, which lead to accumulation of DNA mutations. The use of thyrosine kinase inhibitors targeting the Philadelphia chromosome have enormously improved the treatment of blast crisis, nonetheless resistant patients are still a medical challenge. Yotaro Ochi and collegues used Whole Exome Sequencing of paired chronic phase and blast crisis samples to depict the genetic landscape of progression from the first to the second stage of the disease (as illustrated in their figure). Their results were published in Nature Communication on this May 2021. They used a dataset previously deposited at the EGA (EGAS00001003071) and their new generated data have been made available under accession number EGAS00001005075. Their analysis of the occurring mutations contribute to understanding the mechanisms of CML evolution and therefore develop a protocol for early management of patients with a TKI resistance signature. Up to date, the EGA hosts 99 clonal evolution studies, developed in several cancer types, including myeloma, renal carcinomas and ovarian cancer, in addition to various leukaemia subtypes, where this approach has been more widely applied and produced important results and seminal papers. From a pan-cancer point of view, the definition of tumour architecture through clonal evolution studies is instrumental to unravel the mechanisms of disease progression and treatment-resistance insource. At the EGA, we are honoured to contribute to exciting and important science advances with our service!

  Blog the-last-addition-to-the-list-of-clonal-evolution-studies-in-the-ega

• High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube

  High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. To provide insights into the origins of HGSOC, we We performed whole-exome sequence and copy number analyses of laser-capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients with HGSOC. The majority of tumor-specific sequence and structural alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN genes. An eEvolutionary analyseis revealed that p53 signatures and STICs were are the precursors of ovarian carcinoma which in turn gave rise to metastatic lesionsand identify a. In one patient we identified a second STIC as a metastasis in the fallopian tube opposite from the affected ovary. These analyses revealed a window of seven years between the development of a STIC and the initiation of ovarian carcinomas, with development of metastases following rapidly thereafter. Our results provide insights into the etiology of ovarian cancer and have implications for the prevention, early detection and therapeutic intervention of this disease.

  Study EGAS00001002589

• METABRIC: Data from Batra et al (2021); DNA methylation landscapes of 1538 breast cancers reveal a replication-linked clock, epigenomic instability and cis-regulation

  DNA methylation is aberrant in cancer, but the dynamics, regulatory role and clinical implications of such epigenetic changes are still poorly understood. Here, RRBS-based profiles of 1538 breast tumors and 244 normal breast tissues from the METABRIC cohort are reported, facilitating detailed analysis of DNA methylation within a rich context of genomic, transcriptional, and clinical data. Tumor methylation from immune and stromal signatures are deconvoluted leading to the discovery of a tumor replication-linked clock with genome-wide methylation loss in non-CpG island sites. Unexpectedly, methylation in most tumor CpG islands follows two replication-independent processes of gain (MG) or loss (ML) that we term epigenomic instability. Epigenomic instability is correlated with tumor grade and stage, TP53 mutations and poorer prognosis. After controlling for these global trans-acting trends, as well as for X-linked dosage compensation effects, cis-specific methylation and expression correlations are uncovered at hundreds of promoters and over a thousand distal elements. Some of these targeted known tumor suppressors and oncogenes. In conclusion, the study demonstrates that global epigenetic instability can erode cancer methylomes and expose them to localized methylation aberrations in-cis resulting in transcriptional changes seen in tumors.

  Study EGAS00001004327

• The Molecular Landscape of Asian Breast Cancers Reveals Clinically Relevant Population-Specific Differences

  Molecular profiles of breast cancer have contributed to an improved understanding of the disease, enabled development of molecular prognostic signatures to guide treatment decisions and unveiled new or more accurate therapeutic options for breast cancer patients. However, the extent to which differences in genetic, environmental and lifestyle factors influence molecular profiles in different populations remains poorly characterised, as relatively few large-scale molecular studies of breast tumours in non-Caucasian populations have hitherto been reported. Here, we present the molecular profiles of 560 Asian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to the breast tumours in predominantly Caucasian women reported in TCGA and METABRIC, we show an increased prevalence of Her2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. Using gene expression and immunohistochemistry, we observed elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst Her2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil new opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.

  Study EGAS00001004518