3773 results for "*oma"

in 37.98 milliseconds.

• Single-cell multi-omics of relapse/refractory multiple myeloma patients (Hipo K08K/H067/K43R)

  Therapy resistance in cancers is ingrained in complex clonal dynamics. While the major clonal population in a tumour might respond well to the employed intervention, minor clones will eventually mutate, consequently acquiring a selective advantage and drug resistance. Hence, to improve cancer therapy, it is crucial to understand the mechanisms behind clonal evolution. Here, we applied single-cell transcriptomics and epigenomics, as well as whole-genome sequencing to 15 patients with relapsed/refractory multiple myeloma (RRMM). By profiling longitudinal samples throughout varying treatment regimens, we were able to interrogate patterns of evolution across patients. In particular, by defining clones based on copy number aberrations (CNAs), we found evidence for the majority of clones being diminished but not fully eradicated during treatment.

  Study EGAS00001006538

• Single cell RNA sequencing of relapsed/refractory multiple myeloma

  Study EGAS00001004805

• Integrated genomic analyses reveal molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma

  Atezolizumab (anti–programmed death-ligand 1 [anti-PD-L1]) and bevacizumab (anti-vascular endothelial growth factor [anti-VEGF]) combination therapy has become the new standard of care in patients with unresectable hepatocellular carcinoma. However, potential predictive biomarkers and mechanisms of response and resistance remain less understood. We report integrated molecular analyses of tumor samples from 358 patients enrolled in the GO30140 phase 1b or IMbrave150 phase 3 trials who were treated with atezolizumab combined with bevacizumab, atezolizumab alone, or sorafenib. Pre-existing immunity assessed by high expression of CD274 (PD-L1 mRNA), T-effector signature, and intratumoral CD8+ T cell density were associated with response and better clinical outcomes with the combination treatment. Less clinical benefit was associated with high regulatory T cell (Treg) to effector T-cell ratio and high expression of oncofetal genes such as GPC3 and AFP. Improved outcomes from the combination vs atezolizumab alone appeared to be associated with high expression of KDR (VEGFR2), Treg, and myeloid inflammation signatures, indicating anti-VEGF may contribute by targeting these axes. These findings were further validated by transcriptome analysis of paired pre- and post-treatment biopsies, in situ analysis by multiplex IHC and digital pathology, and in vivo study of an immunogenic hepatocellular carcinoma mouse model. Our findings highlight that anti-VEGF therapy might augment antitumor immunity and enhance anti–PD-L1 immunotherapy by targeting VEGF-mediated angiogenesis, Treg proliferation, and myeloid cell inflammation. Furthermore, our study identified candidate biomarkers for predicting response and resistance to anti–PD-L1 and anti-VEGF combination therapy.

  Study EGAS00001005503

• Methylome of medulloblastoma data (MB_COMICS cohort)

  Study EGAS00001007815

• BLUEPRINT DNA Methylation 450K data of mantle cell lymphoma

  We have applied an analytic strategy to decipher the DNA methylome of 86 mantle cell lymphomas (MCL) in light of the methylome of the entire B-cell lineage. In this way, we first identified two MCL subgroups that respectively carry epigenetic imprints of pre- and post-germinal center B cells. Secondly, we observed that pure tumor-specific changes are rare, as most (89-99%) DNA methylation alterations in MCL are within or in close proximity of those regions showing dynamic methylation in normal B cells. Several thousand of these differentially methylated regions in MCL show concurrent changes in enhancer-associated histone modifications, including a region located 650 Kb away from the MCL oncogene SOX11. At the clinical level, epigenetic and genetic changes co-evolve during MCL progression and the magnitude of epigenetic changes is associated with overall survival of the patients.

  Study EGAS00001001637

• HumanMethylation450K data from Purified Plasma Cells of Monoclonal gammopathy of unknown significance and Multiple myeloma patients and Healthy donors

  HumanMethylation450K data from Purified Plasma Cells of Monoclonal gammopathy of unknown significance and Multiple myeloma patients and Healthy donors

  Study EGAS00001000841

• Evolutionary Genome Analysis of Transformation into Small Cell Carcinomas from Lung Adenocarcinomas

  Anecdotal case have been reported lung adenocarcinoma could occasionally transform into small cell carcinoma. Most of the reported cases were EGFR-mutant lung adenocarcinomas that transform into small cell carcinoma during EGFR tyrosine kinase inhibitor treatment. However, some cases also indicate lung adenocarcinomas without EGFR mutation could also transform into small cell carcinomas. Here we investigate this transformation process by whole genome sequencing of transformed small cell carcinomas as well as serially acquired samples of lung adenocarcinoma into small cell carcinomas.

  Study EGAS00001001757

• Comprehensive genomic profiling of matched glioblastoma tumours, cell-lines, and xenografts reveals genomic stability and adaptation to disparate growth environments

  The mandate of this project was to use drug screening to deliver new drugs for glioblastoma (GBM) to clinical trials, and perform genomic assessment of GBM to discover new therapeutic targets and predictors of response. The sequencing data in this set was derived from GBM patient tumor samples, matched brain tumor initiating cells lines (BTICs), and tumor tissue derived from orthotopic implants.

  Study EGAS00001002709

• Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis.

  Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.

  Study EGAS00001000750

• Association of Age at Diagnosis and Genetic Mutations in Patients with Neuroblastoma

  Neuroblastoma is diagnosed over a wide age range from birth through young adulthood, and older age at diagnosis is associated with a decline in survivability. We performed whole genome sequencing of DNA from diagnostic tumors and their matched germlines from 40 patients with metastatic neuroblastoma obtained between 1987 and 2009. To identify genetic lesions that are associated with age at diagnosis in patients with metastatic neuroblastoma. Age groups at diagnosis included infants (0-18 months), children (18 months-12 years), and adolescents and young adults (>12 years). To confirm the findings from this discovery cohort, validation testing using tumors from an additional 64 patients obtained between 1985 and 2009 was also performed. Formalin-fixed paraffin-embedded tumor tissue was used for immunohistochemistry and fluorescent in situ hybridization. Telomere lengths were analyzed using the whole genome sequencing data, quantitative polymerase chain reaction and fluorescent in situ hybridization

  Study EGAS00001000213