16624 results for "sec+and+unspecified+malignant+neoplasm"

in 39.81 milliseconds.

• Single cell whole genome sequencing of luminal breast epithelial cells from wildtype and BRCA mutation carriers

  Single cell whole genome sequencing was done using DLP+ (https://doi.org/10.1016/j.cell.2019.10.026) on luminal breast epithelial cells from wildtype and BRCA mutation carriers. Each BAM file is a merged BAM from single cells from a single sample, and the cells can be uniquely identified by their @RG group. Only high quality cells were kept, thus there are large differences in BAM sizes. The same sample/patient can be found across multiple BAM files to accumulate more cells, sometimes the same patient will have multiple FACS sorted cell types also split by BAMs.

  Dataset EGAD50000000883

• Health Information National Trends Survey-SEER (HINTS-SEER)

  HINTS-SEER is a cross-sectional survey that sampled cancer survivors from three different SEER cancer registries. Sampling frames of survivors from each registry were stratified by time since diagnosis and race/ethnicity, with non-malignant tumors and non-melanoma skin cancers excluded. Respondents who consented completed a self-administered questionnaire sent through the mail and resulted in a total sample of 1,234 respondents. The goal of HINTS-SEER was to better understand the communication needs and practices, information preferences, risk behaviors and cancer knowledge of cancer survivors using a modified version of the Health Information National Trends Survey (HINTS) specifically designed for cancers survivors. Demographic information on the survivors showed that over 60% of the sample was 10 or more years since diagnosis with the most common cancers being male reproductive (24.6%), female breast (23%) and melanoma (9.6%) and gastrointestinal (8.6%). De-identified data is available in SAS, SPSS, and STATA formats, as part of a data package that also includes a history document, methodology report, data analysis recommendations, and a codebook.

  Study phs004065

• Ovarian cancer organoid biobank

  Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a novel protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing the spectrum of ovarian neoplasms, including non-malignant borderline tumors, as well as mucinous, clear-cell, endometrioid, low- and high-grade serous carcinomas. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and inter-patient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.

  Study EGAS00001003073

• Combined clinical and gene expression score identifies high-risk individuals among follicular lymphoma patients on immunotherapy

  Follicular lymphoma (FL) is usually an indolent malignant B-cell lymphoma, but at least 30% of the patients experience transformation to Diffuse Large B-cell Lymphoma (DLBCL) with inferior survival. Early identification of patients with poor prognosis is essential for tailoring treatment. Here, we describe a network-based integrative analysis of 168 FL-biopsies from 127 patients with long clinical follow-up and transformation status. A distinct shift in expression towards a DLBCL expression phenotype is observed in BTK associated genes in cases with transformation. This shift is present years prior to transformation. An integrated score combining the BTK score and a clinical index is proposed, termed the BTK-FLIPI score. It identifies patients (16%) with very poor prognosis, with median time to progression 21.7 months (95% CI: 14.3-42.6) versus 70.9 months (95% CI: 41.5-95.0) for the remainder. The results suggest BTK as a potential target for treatment of high-risk FL-patients.

  Study EGAS00001002566

• Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia

  Mesenchymal niche cells may drive tissue failure and malignant transformation in the hematopoietic system but the molecular mechanisms and their relevance to human disease remain poorly defined. We demonstrated that perturbation of mesenchymal cells in a mouse model of the preleukemic disorder Shwachman-Diamond syndrome induces mitochondrial dysfunction, oxidative stress and activation of DNA damage responses in hematopoietic stem and progenitor cells. In this study we demonstrate, through massive parallel RNA sequencing of highly purified mesenchymal cells in a range of human preleukemic syndromes, TP53-S100A8/9-TLR4 inflammatory signaling as a common driving mechanism of genotoxic stress, which could be attenuated by TLR4 blockade. S100A8/9 expression in mesenchymal cells predicted outcome in myelodysplastic syndromes, the principal human preleukemic condition, independent of known prognostic variables. Collectively, findings reveal a concept of mesenchymal niche-induced genotoxic stress in heterotypic stem and progenitor cells through inflammatory signaling as an actionable determinant of disease outcome in human preleukemia. The data further provide novel conceptual and mechanistic insights into the intimate link between inflammation and cancer.

  Study EGAS00001001926

• Spatial transcriptomics reveal topological immune landscapes of Asian head and neck angiosarcoma

  Angiosarcomas are rare malignant tumors of the endothelium, arising commonly from the head and neck region (AS-HN) and recently associated with ultraviolet (UV) exposure and human herpesvirus-7 (HHV-7) infection. We examined 81 cases of angiosarcomas, including 47 cases of AS-HN, integrating information from whole genome sequencing, gene expression profiling and spatial transcriptomics (10X Visium). In the AS-HN cohort, we observed recurrent somatic mutations in CSMD3 (18%), LRP1B (18%), MUC16 (18%), POT1 (16%) and TP53 (16%). UV-positive AS-HN harbored significantly higher tumor mutation burden (TMB) than UV-negative cases (p=0.0294). NanoString profiling identified three clusters with distinct tumor inflammation signature (TIS) scores (p<0.001). Spatial transcriptomics revealed topological profiles of the tumor microenvironment, identifying dominant but tumor-excluded inflammatory signals in “immune-hot” cases and immune foci even in otherwise “cold” cases. In conclusion, spatial transcriptomics reveal the tumor immune landscape of angiosarcoma, and in combination with multi-omic information, may improve implementation of treatment strategies.

  Study EGAS00001007083

• Single cell RNA sequencing of colorectal cancer patients (KUL5)

  All libraries were sequenced on Illumina NextSeq or NovaSeq6000 until sufficient saturation was reached.

  Dataset EGAD00001008585

• Mechanism of Decitabine response in MDS/AML patients

  The dataset includes single cell RNA sequencing data from 17 AML/MDS patients undergoing a decitabine clinical trial. In total 47 samples were interrogated using 10X genomics ChromiumTM 140 Single Cell 5' Reagent Kit. The dataset includes bam files for each sample generated using CellRanger with default parameters.

  Dataset EGAD50000001354

• Long read microbiome whole metagenome sequencing

  Long read microbiome whole metagenome sequencing of pediatric GI samples.

  Dataset EGAD50000000486

• Sequencing data for oesophageal and related samples - Abbas et al (WGS)

  Data supporting: "Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma" Abbas et al (WGS for 1397 samples)

  Dataset EGAD00001011196

• WES_WGS_RNAseq

  This dataset includes WES, WGS, and RNAseq data generated from autopsy samples.

  Dataset EGAD00001009499

• Exploring the driver events of eccrine poromas and porocarcinomas: A retrospective, cross-institutional study of 90 cases

  Eccrine poroma (EP) and porocarcinoma (EPC) are rare benign and malignant adnexal neoplasms of the terminal sweat gland duct, respectively. Both can arise de novo, however, EPCs can also arise from a pre-existing EP. To-date, genetic investigation of these tumors has involved studies with small sample sizes and/or limited analyses. To comprehensively compare the driver events and mutational landscape of these tumors, we performed a retrospective multi-institutional whole-exome sequencing and RNA sequencing study on the largest cohort of EPs and EPCs to-date (n=90). We uncovered novel events and delineated different pathways of tumorigenesis underlying these tumors, with EPs driven largely by fusion genes, and EPCs driven largely by somatic mutations, with rare YAP1 and frequent PAK gene novel fusions.

  Dataset EGAD00001015378

• Exploring the driver events of eccrine poromas and porocarcinomas: A retrospective, cross-institutional study of 90 cases

  Eccrine poroma (EP) and porocarcinoma (EPC) are rare benign and malignant adnexal neoplasms of the terminal sweat gland duct, respectively. Both can arise de novo, however, EPCs can also arise from a pre-existing EP. To-date, genetic investigation of these tumors has involved studies with small sample sizes and/or limited analyses. To comprehensively compare the driver events and mutational landscape of these tumors, we performed a retrospective multi-institutional whole-exome sequencing and RNA sequencing study on the largest cohort of EPs and EPCs to-date (n=90). We uncovered novel events and delineated different pathways of tumorigenesis underlying these tumors, with EPs driven largely by fusion genes, and EPCs driven largely by somatic mutations, with rare YAP1 and frequent PAK gene novel fusions.

  Dataset EGAD00001015376

• Exploring the driver events of eccrine poromas and porocarcinomas: A retrospective, cross-institutional study of 90 cases

  Eccrine poroma (EP) and porocarcinoma (EPC) are rare benign and malignant adnexal neoplasms of the terminal sweat gland duct, respectively. Both can arise de novo, however, EPCs can also arise from a pre-existing EP. To-date, genetic investigation of these tumors has involved studies with small sample sizes and/or limited analyses. To comprehensively compare the driver events and mutational landscape of these tumors, we performed a retrospective multi-institutional whole-exome sequencing and RNA sequencing study on the largest cohort of EPs and EPCs to-date (n=90). We uncovered novel events and delineated different pathways of tumorigenesis underlying these tumors, with EPs driven largely by fusion genes, and EPCs driven largely by somatic mutations, with rare YAP1 and frequent PAK gene novel fusions.

  Dataset EGAD00001015377

• Exploring the driver events of eccrine poromas and porocarcinomas: A retrospective, cross-institutional study of 90 cases

  Eccrine poroma (EP) and porocarcinoma (EPC) are rare benign and malignant adnexal neoplasms of the terminal sweat gland duct, respectively. Both can arise de novo, however, EPCs can also arise from a pre-existing EP. To-date, genetic investigation of these tumors has involved studies with small sample sizes and/or limited analyses. To comprehensively compare the driver events and mutational landscape of these tumors, we performed a retrospective multi-institutional whole-exome sequencing and RNA sequencing study on the largest cohort of EPs and EPCs to-date (n=90). We uncovered novel events and delineated different pathways of tumorigenesis underlying these tumors, with EPs driven largely by fusion genes, and EPCs driven largely by somatic mutations, with rare YAP1 and frequent PAK gene novel fusions.

  Dataset EGAD00001015379

• Evolutionary trajectories of IDH-mutant astrocytoma identify molecular grading markers related to cell cycling

  To study the evolutionary processes that drive malignant transformation in IDH-mutant astrocytomas, we performed multi-omics on a large cohort of matched initial and recurrent tumor samples. We find that genome-wide DNA-methylation levels decreased over time, mainly in patients with high-grade recurrences. DNA-demethylation was lifted from specific loci associated with DNA replication, and was associated with upregulation of cell cycling associated genes. Upregulation of cell cycling genes occurred predominantly in proliferating tumor cells, and was associated with tumor grade. Temporal DNA-demethylation and upregulation of cell cycling were hardly affected by chemo- and/or radiotherapy, indicating treatment does not affect the course of disease. Further, we defined a DNA-methylation based signature associated with tumor grade and poor prognostic genetic events, with a prognostic power stronger than CDKN2A/B deletion. We validated its prognostic power on primary tumor samples of patients included in the CATNON randomized phase 3 clinical trial. Therefore this model can serve as a molecular grading marker for IDH-mutant astrocytomas.

  Study EGAS00001007527

• The evolution of hematopoietic cells under cancer therapy

  Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs showed the mutational footprint of these drugs, indicating that non-malignant blood cells received chemotherapy mutations. No trace of 5-fluorouracil (5FU) mutational signature was found in AML secondary to exposure to 5FU, suggesting that cells establishing the AML were quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determined that secondary AMLs began their clonal expansion after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with a clonal expansion that predates the exposure to the cytotoxic agent.

  Study EGAS00001005234

• Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways

  Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In this study we analyze heterochromatin and transcriptomic changes occurring at genes and TEs in HSCs from chronic myelomonocytic leukemia, a severe myeloid malignancy affecting the elderly, compared to age-matched cells, and in the presence or absence of a combination of epidrugs.

  Study EGAS50000000688

• Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways

  Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In this study we analyze heterochromatin and transcriptomic changes occurring at genes and TEs in HSCs from chronic myelomonocytic leukemia, a severe myeloid malignancy affecting the elderly, compared to age-matched cells, and in the presence or absence of a combination of epidrugs.

  Study EGAS50000000367

• Gene expression adaptation of metastases to their host tissue

  The adaptation of metastatic cells to their host tissue critically determines the pathogenicity of a cancer and therefore patient survival. Yet, it remains elusive to what extent the host environment drives gene expression programs in metastatic cells. Here we identify adaptive mechanisms that enable metastases to establish themselves in a novel tissue context. We performed single-cell RNA-sequencing on malignant and benign tissue samples from untreated donors with colorectal adenocarcinoma and liver metastasis to deduce tissue adaptive expression patterns. A novel computational approach identified genes and pathways that consistently adapted to the host tissue at the transition from the primary tumor to the paired metastasis across donors. This analysis revealed that the majority of expression changes in the metastasis reflect an expression signature reminiscent of benign liver epithelial cells. Cellular processes adapting to the liver environment include basic cellular functions such as energy metabolism, as well as tissue-specific pathways such as the regulation of lipid metabolism by PPAR-α. These adaptations potentially increase the pathogenicity of the metastatic cells and may provide new therapeutic strategies.

  Study EGAS50000000817

• Population_dynamics_in_abnormal_haematopoiesis

  Background: Our recent study has made direct insight into the clonal dynamics of blood cell production in an unperturbed setting in a human. Using whole genome sequencing to track acquired somatic mutations, we were able to construct a phylogenetic tree of different stem and progenitor cells and used this tree to determine the dynamics of mature blood cell production in longitudinal samples. These data set the baseline for understanding population dynamics in abnormal haematopoiesis, and how malignant clones outcompete their normal counterparts to drive haematological malignancies. Aim: This study will measure population dynamics in abnormal human haematopoiesis in patients with clonal blood stem cell disorders. Methods: From patient bone marrow or peripheral blood, we have isolated colonies grown from single blood stem cells/progenitors. Colony DNA will be analysed by whole-genome sequencing to build (or populate) a phylogenetic tree to determine clonal relationships and track stem cell contribution to mature blood cell production. These data will also reveal disease-associated genomic features (mutational burden and mutational signatures) in haematopoietic cells.

  Study EGAS00001003181

• Test dataset with ligh-weight files

  This is a test dataset derived from public data of the 1000 Genomes Project. Its purpose is not to allow for any inference about cohort data or results, but to aid bioinformaticians in the technical development and testing of tools, as well as data consumers in learning how to access information. This dataset consists of 3 pairs of light-weight (sliced) files: BAM + BAI, CRAM + CRAI and VCF + TBI. These files can be downloaded directly through the EGA-download-client PyEGA3 (https://github.com/EGA-archive/ega-download-client). For any further questions, please contact the DAC (Helpdesk - email: helpdesk [at] ega-archive [dot] org).

  Dataset EGAD00001009826

• TK-EP862 - Patient-derived xenograft model of Posterior Fossa A Ependymoma - WSG data

  In Vivo Loss of Tumorigenicity in a Patient-Derived Orthotopic Xenograft Mouse Model of Ependymoma. Whitehouse et al. 2023 Frontiers in Oncology. We describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) EPN, derived from a metastatic cranial lesion. Patient and PDOX tumors were analyzed using RNA sequencing. WSG data (paired end) provided here correspond to germline DNA, Surgical sample 4 (described in the above manuscript as a cranial metastasis of PFA ependymoma), and a patient-derived xenograft derived from the patient.

  Dataset EGAD00001010008

• Single Cell RNASeq for ARMS tumors

  6 samples from 3 mice related to Alveolar Rhabdomysarcoma. In this study, we employ scRNA-seq to analyze ARMS tumors from a conditional mouse model of ARMS. The conditional knock-in mouse model of ARMS, in which the Pax3-Foxo1 allele is activated in the skeletal muscle cell lineage via Myf6Cre (Myf6CrePax3P3Fm/P3FmTrp53F2-10/F2-10; referred to hereafter as GEMM-ARMS) has been described previously23,24. These mice also carry Cre-activated reporters, eYFP to label Pax3::Foxo1-expressing cells and dsRED2 to labels Myh2-expressing cells. Some tumors are derived from GEMM-ARMS mice, and some are allografts of GEMM-ARMS tumors into immunodeficient mice

  Dataset EGAD50000002241

• Analysis of DNA methylation in normal B cells and chronic lymphocytic leukemia

  Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes.As second study using these samples focued on evolution and resulting intra-tumor heterogeneity in CLL. We used 450k bead-chip arrays to study DNA methylomes in 68 chronic lymphocytic leukemia (CLL) cases, including 28 serial cases. The result establishs linked evolution of epigenetic and genetic alterations in progressive disease, revealing an important aspect of the biology of epigenetics in cancer.

  Study EGAS00001000534