4772 results for "*oma"

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• Intellance-2: omics data on recurrent glioblastoma patients participating in the Intellance-2 clinical trial, prior to treatment.

  This study contains omics data from patients from the Intellance-2 clinical trial, in which effectiveness of ABT414 in EGFR amplified recurrent glioblastoma patients was tested. Patients were randomly assigned to one of three arms: (1) standard of care treatement (TMZ or CCNU), (2) Only ABT414 and (3) ABT414 + (TMZ|CCNU)

  Study EGAS00001005437

• Tumor-specific expression of let-7i and miR-192 is associated with resistance to cisplatin-based chemoradiotherapy in patients with larynx and hypopharynx cancer

  Background: The majority of patients with locally advanced larynx or hypopharynx squamous cell carcinoma are treated with organ preserving chemoradiotherapy (CRT). Clinical outcome following CRT varies greatly. We hypothesized tumor microRNA (miRNA) expression is predictive for outcome following CRT. Methods: Next-generation sequencing (NGS) miRNA profiling was performed on 37 formalin fixed paraffin embedded (FFPE) tumor samples. Patients with a recurrence free survival (RFS) of less than 2 years (“poor outcome”) and patients without recurrence within 2 years (“good outcome”) were compared by differential expression analysis. Tumor-specific miRNAs were selected based on normal mucosa miRNA expression data from The Cancer Genome Atlas database. A model was constructed to predict outcome using group-regularized penalized logistic ridge regression. Candidate miRNAs were validated in the initial sample set by RT-qPCR as well as in 46 additional tumor samples.Results: 1,938 known mature miRNAs were detected. Thirteen miRNAs were differentially expressed (p<0.05, FDR<0.1) according to outcome group. Initial class prediction in the NGS cohort (n=37) resulted in a model combining five miRNAs and disease stage, able to predict CRT outcome with an area under the curve (AUC) of 0.82. In the RT-qPCR cohort (n=83), 25 patients (30%) experienced early recurrence (median RFS 8 months; median follow-up 42 months). Class prediction resulted in a model combining let-7i-5p and miR-192-5p and disease stage, able to discriminate with an AUC of 0.80 patients with good versus poor clinical outcome.Conclusion: The combined miRNA expression and disease stage prediction model is superior to using either factor alone. ¬¬¬This study indicates NGS miRNA profiling using FFPE specimens is feasible, resulting in clinically relevant biomarkers.

  Study EGAS00001004001

• Host whole genome variations are associated with neurocognitive outcome in survivors of pediatric medulloblastoma

  Host whole genome analysis is a promising source of predictive information for long-term morbidity in cancer survivors. However, studies on genetic predictors of long-term outcome, particularly neurocognitive function following chemoradiation in pediatric oncology are limited. In the present study, we evaluated variations in host whole genome single nucleotide polymorphisms (SNPs) and their association with cognitive outcome. Whole-genome SNP analysis of host peripheral blood was conducted on 22 medulloblastoma long-term survivors, of whom 18 completed neuropsychological testing. First, unsupervised consensus clustering of the most variable SNPs within 409 genes involved in DNA repair was performed. Discrete variant groups were identified, although they were not associated with cognitive outcome, suggesting that variations in genes corresponding to a single functional group may be insufficient to predict long-term outcome alone. In support of this interpretation, unsupervised hierarchical clustering analysis using disease-associated gene variants by cognitive impairment status yielded two distinct variant clusters comprised of 36 variants, 34 of which were in noncoding regions. These findings illustrate for the first time that cognitively impaired survivors have a distinct variant profile compared to other medulloblastoma survivors. Future research in larger cohorts is needed to validate host genome predictors of cognitive impairment that may impact clinical management.

  Study EGAS00001002996

• Microenvironment subtypes and association with tumor cell mutations and antigen expression in follicular lymphoma

  Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the immune microenvironment of FL. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies.

  Study EGAS00001006052

• Reconstruction of complex rearrangement patterns causing the initiation of clear cell renal cell carcinoma.

  The genomic hallmark of clear cell renal cell carcinoma is the loss of the short arm of chromosome three. This appears to be the earliest genomic event in the formation of these cancers. Often chromosome 3 is lost at the same time as part of chromosome 5 is duplicated via an unbalanced translocation, often with features consistent with focal chromothripsis. In this study, we sought to reconstruct the chromothriptic event that underlies the initiation of kidney cancer. We used long read sequencing (promethION, Oxford Nanopore Technologies) of patient tumour-derived DNA to elucidate how a single cell division error can generate cancer genome complexity.

  Study EGAS00001004015

• The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma

  Patients with metastatic uveal melanoma (UM) have an abysmal prognosis. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. Here we test if epigenetic therapy would enhance PD-1 immunotherapy in patients with metastatic UM. We report the results of the PEMDAC phase 2 clinical trial (n=29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic UM. The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Extensive genomics studies were performed using DNA/RNA and single cell sequencing and flow cytometry. Objective responses and prolonged survival were seen in three patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM. Further exploration of combined immunotherapy and epigenetic therapy in metastatic UM is warranted.

  Study EGAS00001005478

• Multi-omics of Richter syndrome

  Richter syndrome (RS) is the aggressive transformation of Chronic Lymphocytic Leukemia, mostly with Diffuse Large B-Cell Lymphoma histology. While histologically similar, RS and de novo DLBCLs present with different clinical courses. We characterized the RS epigenome by combining genome-wide DNA methylation with transcriptome-sequencing on a large RS cohort.

  Study EGAS00001005495

• Cell type-specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics

  We developed a protocol for the separation of esophageal carcinoma tissue into leukocytes (using CD45 as a marker), epithelial cells (EpCAM), and fibroblasts (two out of PDGFRA, CD90, anti-fibroblast) by fluorescence-activated cell sorting followed by RNA-sequencing

  Study EGAS00001004053

• The genomic landscape of early stage ovarian high grade serous carcinoma

  To determine whether early-stage ovarian high grade serous carcinoma (HGSC) represents a distinct genomic entity, we collected samples from 43 patients with stage IA-IIA HGSC to identify potential differences in short genomic variants and copy number aberrations, and compared them to a cohort of 52 late-stage (stage IIIC-IV) cases. We found no significant differences in somatic mutations or focal copy number alterations between early-stage and late-stage cohorts. There was, however, a significant difference in both ploidy and copy number signature exposure between early and late-stage samples, with higher ploidy and signature 4 exposure in late-stage cases. Unsupervised hierarchical clustering revealed three clusters, which were prognostic. Together, our data suggest that early and late-stage HGSC share fundamental genomic features, but that late- stage disease appears distinct from early-stage, with evidence of whole genome duplication that may provide evolutionary benefit.

  Study EGAS00001005567

• The Spatial Heterogeneity in Multiple Myeloma - from the Subclonal Architecture to the Immune Microenvironment (partly hipo_K08K)

  Multiple myeloma (MM) cells show pronounced heterogeneity not only within a given patient but also between spatially separated tumor loci in the bone marrow. Understanding this spatial heterogeneity is emerging as a critical challenge for the successful treatment of the disease. Yet, our understanding of spatial differences in the subclonal architecture, molecular signatures and interactions with the tumor microenvironment remains very limited. To address this shortcoming, we performed bulk and single-cell multi-region sequencing, including random bone marrow samples from the iliac crest and paired imaging-guided focal lesion specimens from 15 newly diagnosed MM patients. We found a median of 5 subclones per patient and unique subclones in focal lesions. Central features of spatial heterogeneity included a consistent down-regulation of the chemoattractant cytokines CXCL7 and CXCL12 in focal lesion tumor cells as well as a significant depletion of macrophages in the focal lesion microenvironment. In contrast, a site-specific expansion of T-cell clones was not detected in focal lesions. In conclusion, our results demonstrate the relevance of considering spatial heterogeneity with potential implications for immunotherapies and molecular studies analyzing the role of gene signatures and MM-microenvironment interactions in disease progression.

  Study EGAS00001006090