4116 results for "*oma"

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• Cerebrospinal fluid cfDNA sequencing for classification of central nervous system glioma

  Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained by surgery or biopsy, cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses. Experimental design: We performed targeted next-generation sequencing (NGS) of CSF cfDNA in a representative cohort of 85 patients presenting with with suspicion of primary or recurrent glioma at two neurooncological centers. Copy-number variation (CNV) profiles, single nucleotide variants (SNVs), and small insertions/ deletions (indels) were combined into a molecular-guided tumor classification. Comparison with the solid tumor was performed for 38 cases with matching solid tissue available. Results: Cases were stratified into four groups: glioblastoma (n = 32), other glioma (n = 19), non-malignant (n = 17) and no confirmed diagnosis available (n = 17). We introduce a molecular-guided tumor classification, enabling identification of tumor entities and/ or cancer specific alterations in 75.0 % (n = 24) of glioblastoma and 52.6 % (n = 10) of other glioma cases. The overlap between CSF and matching solid tissue was highest for CNVs (26-48 %) and SNVs at pre-defined gene loci (44 %), followed by SNVs/indels identified via uninformed variant calling (8-14 %). A molecular-guided tumor classification was made 23.5 % (n = 4) of cases with no confirmed diagnosis available. Conclusions: We developed a workflow for targeted sequencing of CSF cfDNA as well as a strategy for interpretation and reporting of sequencing results based on a molecular-guided tumor classification in glioma.

  Study EGAS50000000060

• noninvasive lung cancer subtyping

  Accurate diagnosis of lung cancer is important for treatment decision-making. Currently, the gold standard for diagnosing histological subtypes of lung cancer relies on tumor biopsies. Recently, liquid biopsy, particularly cell-free DNA (cfDNA), has shown promising results in cancer detection and classification. In this study, we investigated the potential of cfDNA methylome for the noninvasive classification of lung cancer histological subtypes. Specifically, we focused on the two most prevalent lung cancer subtypes, lung adenocarcinoma and lung squamous cell carcinoma. Using a fragment-based marker discovery approach, we identified robust subtype-specific methylation markers from tumor samples. These markers were successfully validated in independent cohorts and associated with subtype-specific transcription activity. Leveraging these markers, we constructed a subtype classification model using cfDNA methylation profiles, achieving an AUC of 0.808 in the cross-validation and an AUC of 0.747 in the independent validation. Additionally, tumor copy number variations inferred from cfDNA methylome analysis revealed potential implications for treatment selection. In summary, our study demonstrates the potential of cfDNA methylome analysis for noninvasively lung cancer subtyping, offering insights for cancer monitoring and early detection.

  Study EGAS00001007717

• Pediatric Low-Grade Glioma RNA and Targeted Sequencing

  Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS/MAPK pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. 84% of cases harbored a driver alteration, while those without an identified alteration also often exhibited up-regulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared to SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.

  Study EGAS00001004242

• DIPG RNA and exome sequencing

  DIPG is a paediatric high-grade glioma that diffusely infiltrates the brainstem and is the leading cause of paediatric brain tumour death. Here we performed RNA and whole exome sequencing on DIPG and control samples to analyse transcriptomic and genetic alterations associated with this devastating disease, and to understand the relationship between them.

  Study EGAS00001004749

• Oesophageal adenocarcinoma RNAseq from LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19)

  This dataset contains bulk transcriptomes from the inoperable cohorts of the LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19). Transcriptomes were prepared from pre-treatment oesophageal tumour biopsies using a ribodepletion approach in order to assess both previously reported (e.g. PD-L1 expression) and novel predictive expression-based biomarkers for immunochemotherapy treatment in this setting. On-treatment and post-treatment biopsies were generated as well to characterize response to therapy, and samples were also prepared from paired normal GI tissues for a subset of patients. scRNA-seq based deconvolution was also applied to bulk transcriptomes in this study to estimate the cell composition of tumour biopsies and assess the link between the presence of specific cell types with immunochemotherapy outcomes.

  Dataset EGAD00001009399

• Oesophageal adenocarcinoma WGS from LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19)

  This dataset contains whole genome sequencing (WGS) generated from the inoperable cohorts of the LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19). WGS data were generated with the aim to assess previously reported (e.g. tumour mutational burden) and novel predictive genomic markers for immunochemotherapy treatment in this setting. Using these data, mutation and copy number profiles were generated for the LUD2015-005 study, which were assessed for correlation with patient outcomes from this trial.

  Dataset EGAD00001009400

• Pediatric HGG WES and RNA-Seq

  Paediatric high-grade glioma (pHGG) is the leading cause of paediatric brain tumour death. Here we performed RNA and whole exome sequencing on pHGG samples to analyse transcriptomic and genetic alterations associated with this devastating disease, and to understand the relationship between them.

  Study EGAS00001005687

• MM GWAS dataset

  This is a meta-analysis of myeloma datasets, both with and without the UK Biobank cohort included.

  Dataset EGAD50000000422

• 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 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 EGAD00001015379

• ExomeSeq Neoantigen Immunogenicity Landscapes

  Immune checkpoint blockade (ICB) therapy is a cornerstone of oncologic treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and other malignancies. Neoantigen immunoediting drives ICB efficacy, yet the fundamental physiochemical characteristics of neoantigens and how neoantigen immunogenicity shapes treatment response remains poorly understood. To help address these questions, a prospective clinical trial of NSCLC patients treated with nivolumab was conducted. We assessed genomic alterations in tumors from 58 patients and performed large-scale neoepitope immunogenicity analyses, before and during treatment (CheckMate153, CA209-153). Tumors were analyzed by whole-exome and transcriptome sequencing. In responding patients, loss of mutation and neoantigen burden early during therapy associated with clinical benefit. We evaluated the immunogenicity of 1,453 candidate neoantigens and identified 502 neopeptides that bound to MHC I and 196 neopeptides that were immunogenically recognized by T cells in the setting of nivolumab treatment. These T cell reactive neoantigens were differentially present in clonal populations that underwent distinctive evolutionary trajectories across responders and nonresponders. Mapping these neoantigens to tumor clonal dynamics and clinical response revealed strong selection against immunogenic neoantigen harboring clones compared to non-immunogenic clones. Using this large collection of neoantigens, we identified position specific amino acid features related to immunogenicity, which we used to develop and validate an immunogenicity score. Changes in the genomic and neoantigen immunogenicity landscapes were accompanied by temporal changes in the tumor microenvironment. Nivolumab-induced microenvironmental evolution in NSCLC shared some similarities with that in melanoma, yet critical differences in immunologic programs were apparent from comparative network analysis between tumor types. This study provides unprecedented molecular portraits of the neoantigen landscapes underlying nivolumab’s mechanism of action.

  Study EGAS00001007508

• RNASeq Neoantigen Immunogenicity Landscape

  Immune checkpoint blockade (ICB) therapy is a cornerstone of oncologic treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and other malignancies. Neoantigen immunoediting drives ICB efficacy, yet the fundamental physiochemical characteristics of neoantigens and how neoantigen immunogenicity shapes treatment response remains poorly understood. To help address these questions, a prospective clinical trial of NSCLC patients treated with nivolumab was conducted. We assessed genomic alterations in tumors from 58 patients and performed large-scale neoepitope immunogenicity analyses, before and during treatment (CheckMate153, CA209-153). Tumors were analyzed by whole-exome and transcriptome sequencing. In responding patients, loss of mutation and neoantigen burden early during therapy associated with clinical benefit. We evaluated the immunogenicity of 1,453 candidate neoantigens and identified 502 neopeptides that bound to MHC I and 196 neopeptides that were immunogenically recognized by T cells in the setting of nivolumab treatment. These T cell reactive neoantigens were differentially present in clonal populations that underwent distinctive evolutionary trajectories across responders and nonresponders. Mapping these neoantigens to tumor clonal dynamics and clinical response revealed strong selection against immunogenic neoantigen harboring clones compared to non-immunogenic clones. Using this large collection of neoantigens, we identified position specific amino acid features related to immunogenicity, which we used to develop and validate an immunogenicity score. Changes in the genomic and neoantigen immunogenicity landscapes were accompanied by temporal changes in the tumor microenvironment. Nivolumab-induced microenvironmental evolution in NSCLC shared some similarities with that in melanoma, yet critical differences in immunologic programs were apparent from comparative network analysis between tumor types. This study provides unprecedented molecular portraits of the neoantigen landscapes underlying nivolumab’s mechanism of action.

  Study EGAS00001007509

• Cancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis

  Targeted therapy interventions using tyrosine kinase inhibitors (TKIs) provide encouraging treatment responses in ALK-rearranged lung adenocarcinomas, yet resistances occur almost inevitably. Apart from tumor cell-intrinsic resistance mechanisms, accumulating evidence supports a role of cancer-associated fibroblasts (CAFs) in affecting the therapeutic vulnerability of lung cancer cells. Here, we aimed to investigate underlying molecular networks shaping the therapeutic susceptibility of ALK-driven lung adenocarcinoma cells via tumor microenvironmental cues using three-dimensional (3D) spheroid co-culture settings. We show that CAFs promote therapy resistance of lung tumor cells against ALK inhibition by reducing apoptotic cell death and increasing cell proliferation. Using single-cell RNA-sequencing analysis, we show that genes involved in lipogenesis constitute the major transcriptional difference between TKI-treated homo- and heterotypic lung tumor spheroids. CAF-conditioned medium and CAF-secreted factors HGF and NRG1 were both able to promote resistance of 3D-cultured ALK-rearranged lung tumor cells via AKT signaling, which was accompanied by enhanced de novo lipogenesis and supression of lipid peroxidation. Notably, simultaneous targeting of ALK and SREBP-1 was able to overcome the established CAF-driven lipid metabolic-supportive niche of TKI-resistant lung tumor spheroids. Our findings highlight a crucial role of CAFs in mediating ALK-TKI resistance via lipid metabolic reprogramming and suggest new ways to overcome resistance towards molecular directed drugs by targeting vulnerabilities downstream of oncogenic signaling.

  Study EGAS50000000135

• DAC for "Cancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis"

  DAC for the data of "Cancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis" with: • Holger Sültmann • h.sueltmann@dkfz.de • German Cancer Research Center (DKFZ) • Ann-Kathrin Daum • a.daum@dkfz.de • German Cancer Research Center (DKFZ)

  Dac EGAC50000000076

• Small-RNA sequencing of pheochromocytoma and paraganglioma arising from germline SDHB mutations

  Single-end 75 basepair small-RNA sequencing of 90 SDHB-deficient non-metastatic and metastatic pheochromocytoma and paraganglioma. Samples were prepared using the NEXTFLEX® Small RNA-Seq Kit v3 (Bioo Scientific ). Samples were sequenced at the molecular genomics core (Peter MacCallum Cancer Centre) using 50bp single end sequencing on the Illumina NextSeq 500 (Illumina, USA). This dataset contains raw sequencing reads in FASTQ format.

  Dataset EGAD50000000501

• Whole genome sequencing of pheochromocytoma and paraganglioma arising from germline SDHB mutations

  Paired-end 150 basepair whole genome sequencing of 94 SDHB-deficient non-metastatic and metastatic pheochromocytoma and paraganglioma. Libraries were prepared using the Illumina® TruSeq™ DNA Nano library preparation method according to the manufacturer’s instructions at The University of Melbourne Centre for Cancer Research (UMCCR) using 200ng input DNA and a 550 base pair insert size. Samples were sequenced in separate batches on the Illumina® Nova-Seq 6000 according to manufacturer’s instructions (Illumina, USA). Included in this dataset are FASTQ format files containing raw read data, CRAM format files containing reads aligned to GRCh38, and VCF format files containing germline variants calls.

  Dataset EGAD50000000502

• Single-nuclei ATAC sequencing of pheochromocytoma and paraganglioma arising from germline SDHB mutations

  10x genomics single-nuclei ATAC sequencing of 7 SDHB-deficient non-metastatic and metastatic pheochromocytoma and paraganglioma, and 1 normal adrenal medulla sample. snATAC-seq was conducted using the "Van Helsing" protocol (dx.doi.org/10.17504/protocols.io.bw52pg8e). Once processed, snATAC-seq libraries were sequenced on the Illumina NextSeq 500 (Illumina, USA) using 50bp paired-end sequencing. Raw sequencing data in BCL format was demultiplexed using cellranger-atac mkfastq (V2.0.0). This dataset contains sequencing reads in FASTQ format. R1/R3 files contain the forward and reverse sequencing reads, respectively, R2 contains the 10x Barcode.

  Dataset EGAD50000000503

• Whole transcriptome sequencing of pheochromocytoma and paraganglioma arising from germline SDHB mutations

  Paired-end 150 basepair whole transcriptome sequencing of 91 SDHB-deficient non-metastatic and metastatic pheochromocytoma and paraganglioma. Samples were prepared using the NEB-Next directional RNA-Seq kit (NEB, USA) and underwent 150bp paired-end sequencing on the Illumina NovaSeq 6000 (Illumina, USA) according to manufacturer’s instructions. This dataset contains raw sequencing reads in FASTQ format.

  Dataset EGAD50000000504

• Single-nuclei RNA sequencing of pheochromocytoma and paraganglioma arising from germline SDHB mutations

  10x genomics single-nuclei RNA sequencing of 9 SDHB-deficient non-metastatic and metastatic pheochromocytoma and paraganglioma. snRNA-seq was performed using the ‘Frankenstein’ protocol (dx.doi.org/10.17504/protocols.io.bqxymxpw). Briefly, nuclei were extracted from frozen tissues and subjected to fluorescence-activated nuclei sorting (FANS) using 4′,6-diamidino-2-phenylindole (DAPI). Sorting was performed using a BD FACSaria 2 instrument, sorting between 3000 and 10,000 nuclei per sample, capturing both diploid and tetraploid populations. FAN-sorted nuclei were immediately processed using either the 10x Chromium Single Cell 5’ (PN-1000006, 4 samples) or 3’ (PN-1000075, 4 samples) Library & Gel Bead Kit (10x Genomics, USA). Once processed, snRNA-seq libraries were sequenced on the Illumina Nova-Seq 6000 (Illumina, USA) using 150bp paired-end sequencing. This dataset contains raw sequencing reads in FASTQ format.

  Dataset EGAD50000000505

• IDH mutant Glioma methylation analysis and prognostic signatures

  Study EGAS00001006961

• Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome

  Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas and characterize its features using multi-omics profiling. We aim to deepen the knowledge about the biology and clinical features of ALT-positive neuroblastomas by enriching ALT tumors in the study cohort independent of ATRX mutation status. Using a combination of genomic, transcriptomic and proteomic profiling, we provide evidence that this subgroup is clinically and molecularly distinct.

  Study EGAS00001004349

• Cergentis FFPE-TLC sequencing of colorectal carcinoma

  In this study, formalin-fixed paraffin-embedded targeted locus capture (FFPE-TLC) sequencing is used as a novel technology for targeted detection of tumor-specific genomic structural variants (SVs) in the primary tumor of 29 colorectal cancer patients with metastatic disease. The tumor region was macrodissected and sequenced for 29 patients, and the "normal" region of the same slide was macrodissected and sequenced for 8 of these patients. SVs were found in the common fragile site (CFS)-associated genes MACROD2, PRKN, FHIT and WWOX as well as SVs caused by three LINE transposable elements. Tumor-specificity of selected SVs was independently verified by droplet digital PCR of tumor tissue DNA and their applicability as plasma circulating tumor DNA biomarkers was demonstrated. This dataset contains the hg19 reference alignment of the FFPE-TLC sequences for all 29 colorectal cancers and 8 adjacent normals.

  Dataset EGAD50000000618

• Biomarker Screen for Efficacy of Oncolytic Virotherapy in Patient-derived Pancreatic Cancer Cultures

  Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking. We screened fourteen patient-derived PDAC cultures for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H 1PV using live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays. Sensitivity was correlated with transcriptome profiles to identify potential predictive biomarkers for response to OVT. Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the basal-like molecular subtype, the quasi-mesenchymal subtype of PDAC was more sensitive to H-1PV, jin-3, and T-VEC. Expression of viral entry receptors did not correlate with sensitivity to OV treatment. Rather, cellular pathways controlling immunological, metabolic, and proliferative signalling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas cGAS expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures.

  Study EGAS00001007001