4901 results for "*oma"

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• Malignant progression of an ancestral bone marrow clone harboring a CIC-NUTM2A fusion in isolated myeloid sarcoma

  Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute myeloid leukemia (AML) or, in the absence of bone marrow involvement. We identified an infant with isolated myeloid sarcoma whose bone marrow was negative for involvement by flow cytometry. Sequencing revealed the fusion oncogene CIC-NUTM2A and identified the sarcoma to be clonally evolved from the bone marrow which carried the fusion despite the absence of pathology. Murine modeling confirmed the ability of the fusion to transform hematopoietic cells and identified receptor tyrosine kinase signaling activation consistent with disruption of the CIC transcriptional repressor. These findings extend the definition of CIC-rearranged malignancies to include hematologic disease, provide insight into the mechanism of oncogenesis, and demonstrate the importance of molecular analysis and tracking of bone marrow involvement over the course of treatment in myeloid sarcoma, including patients that lack flow cytometric evidence of leukemia at diagnosis.

  Study EGAS00001006833

• Single cell RNA sequencing of bone marrow mononuclear cells

  Bone marrow aspirates were obtained from patients with relapsed/refractory large B cell lymphoma (rrLBCL), mononuclear cells isolated by ficoll density-gradient centrifugation, and loaded onto a 10X Chromium for single cell RNA-sequencing using 5’ chemistry without prior cryopreservation. Healthy donor bone marrow mononuclear cells were obtained from healthy allogeneic stem cell transplant donors and analyzed following viable cryopreservation.

  Study EGAS00001006836

• Profiling of childhood neuroblastoma and the immune microenvironment by single-cell sequencing of RNA and TCR

  Neuroblastoma tumor cells and their tumor microenvironment are studied by single-cell RNA sequencing of primary neuroblastoma tumors and neuroblastoma-infiltrated tissues/metastases. Both diagnostic samples, taken pre-treatment and samples taken after induction chemotherapy at surgical resection and biopsies from relapse samples are included.  For a number of patients single-cell RNA sequencing of blood samples (controls) are included and additionally we performed single-cell T cell receptor sequencing (TCR) on the tumor and blood samples. With this study, we will focus on identifying differences in tumor cells and their (immune) microenvironment 1) before and after treatment or at relapse and 2) between primary tumors and infiltrated tissues/metastases. Moreover, with TCR sequencing we aim to unveil immune cell dynamics in patients with neuroblastoma.

  Study EGAS00001006823

• Y90 radioembolization followed by intravenous Nivolumab for advanced hepatocellular carcinoma

  To evaluate the efficacy of combination therapy with ICI and RT in patients, a Phase II trial (CA209-678) was conducted to investigate the efficacy and safety of Y90-RE followed by nivolumab in patients with advanced HCC (NCT03033446, n = 36). Interestingly, the ORR was found to be 30.6% in all patients and 43.5% when restricted to patients with only intrahepatic tumors, suggesting possible synergism between Y90-RE and ICI. Here we present whole exome sequencing (WES) and RNA-seq data for 33 patients treated with Y90 radioembolization followed with Nivolumab.

  Study EGAS00001006834

• Identification and functional characterisation of a rare MTTP variant underlying familial non-alcoholic fatty liver disease

  We identified a rare causal variant in MTTP, c.1691T>C p.I564T (rs745447480) encoding microsomal triglyceride transfer protein (MTP) causing progressive non-alcoholic fatty liver disease with cirrhosis and hepatocellular carcinoma unrelated to metabolic syndrome, without manifestations of abetalipoproteinemia, in a four generation family with South Asian ancestry. Variant-expressing hepatocyte-like-cells (HLCs) derived from human induced pluripotent stem cells generated from homozygous donor skin fibroblasts had lower lipoprotein ApoB secretion, compared to wild type cells. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, production of reactive oxygen species, delineating the progression of disease associated with homozygosity for MTTP p.I564T

  Study EGAS00001005254

• TK-EPN862 - Patient-dervied xenograft model of Posterior Fossa A Ependymoma - RNAseq

  Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, patients who survive treatment for the most common subtype of pediatric EPN (posterior fossa A (PFA)), often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of PFA EPN, derived from a metastatic cranial lesion. Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo. Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenge in propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models

  Study EGAS00001006844

• Exome sequencing of HCV+ lymphoma

  The present retrospective study aimed to explore the genetic landscape of a well-characterized series of 34 HCV-associated B-cell lymphomas from the observational multicentric ANRS HC-13 Lympho-C Study using tumor and matched germline whole exome sequencing (WES). It reported the first series of VHC-positive lymphoma patients analyzed by WES. Our results provide an overview of the genetic landscape associated to HCV-related B-cell lymphomas and highlight some novel putative candidate genes.

  Study EGAS00001006860

• Molecular evolution of classic Hodgkin lymphoma revealed through whole genome sequencing of Hodgkin and Reed Sternberg cells

  Here we leveraged whole genome structural variant copy number analysis to report the first whole genome sequencing landscape of HRS cells and reconstruct the chronology and likely etiology of pathogenic events prior to the clinical diagnosis of cHL.

  Study EGAS00001006884

• Population_based_analysis_of_POT1_variants_in_a_cutaneous_melanoma_case_control_cohort

  Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumor types, including melanoma, glioma, leukemia and cardioangiosarcoma. We sequenced all coding exons of the POT1 gene in 2,929 European-descent melanoma cases and 3,298 controls, identifying 43 protein-changing genetic variants. We performed functional studies on each of these variants and explored their possible contribution to disease risk.

  Study EGAS00001006870

• WGS of MAPKi acquired resistant samples from patients and PDX models

  Blocking cancer genomic instability, which generates diverse variants that enable rapid adaptations, may prevent tumor escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients and patient-derived xenografts, acquired-resistant genomes of metastatic cutaneous melanoma accumulate amplicons of resistance-driver, non-homologous end-joining (NHEJ), and homologous recombination repair (HRR) genes within complex genomic rearrangements (CGRs) and extrachromosomal circular DNAs (ecDNAs). Also, chromothriptic genomic regions enrich for mutations and may engender ecDNAs and CGRs. Overall, somatic mutations within ecDNA- and CGR-amplicons enrich for HRR signatures, and, in acquired resistance, ecDNA (versus CGR) mutations enrich for APOBEC3 signatures. Breakpoint-sequence analysis suggests NHEJ as critical to double-stranded DNA break repair underlying CGR and ecDNA formation. In vivo, NHEJ-targeting by a DNA-PKCS inhibitor prevented acquired MAPKi-resistance by reducing the size of ecDNAs and CGRs early on combination treatment. Thus, targeting the cause(s), as opposed to the consequences, of genomic instability prevents acquired resistance.

  Study EGAS00001006874