3796 results for "*oma"

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• POT1_splice_site_mutant_analysis

  We are interested in the contribution mutations in the Shelterin complex protein POT1 may have to the development of melanoma. We have identified a patient who carries a splice site mutation in POT1 and as part of our analysis of this gene we aim to sequence the transcriptome of this patient to see how this mutation influences splicing. RNA has been obtained from lymphocytes collected from the patient.

  Study EGAS00001000571

• Whole genome sequencing of metastatic melanomas from a patient with primary resistance to BRAF inhibition

  Here, we investigated the underlying cause of treatment failure in a patient with BRAF mutant melanoma who presented primary resistance. We used whole-genome sequencing (WGS) to characterise five metastatic tumours from a BRAF mutant melanoma patient who presented intrinsic resistance.

  Study EGAS00001000580

• Whole genome sequencing of tumour and normal paired samples of diffuse intrinsic pontine gliomas

  Diffuse intrinsic pontine glioma (DIPG) have a universally dismal prognosis (median 9-12 months), with neither chemotherapeutic nor targeted agents showing any substantial survival benefit in clinical trials in children with these tumours. DIPG are highly infiltrative malignant glial neoplasms of the ventral pons, which due to their location within the brain, make them unsuitable for surgical resection and consequently have a universally dismal clinical outcome. Recent high-throughput sequencing approaches have revealed a striking prevalence of K27M mutations in the genes encoding the histone variants H3.3 (H3F3A) or H3.1 (HIST1H3B) in the childhood brain tumour DIPG. This K-to-M substitution confers a trans-dominant ablation of global H3K27 trimethylation, which likely profoundly alters gene expression through de-repression of polycomb repressive complex 2 (PRC2) target genes. Despite these advances in our understanding of the distinct biology of these tumours, approaches for specific novel therapeutic interventions are not clear, and little has been reported of the secondary mutations accompanying these changes. We carried out whole genome sequencing on a series of 20 tumour normal pairs of pre-treatment biopsy samples of DIPG, for which the patients underwent a safe stereotactic procedure, and whole exome sequencing on a further six tumour normal pairs obtained at autopsy.

  Study EGAS00001000572

• Whole genome sequencing and whole exome sequencing of DIPG tumors and matched normal tissue

  Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling.

  Study EGAS00001000575

• Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma

  Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations inTP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis.

  Study EGAS00001000579

• These are from Korean HCC samples with exome sequencing

  Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in 9 genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodelling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (p = 0.016 and p = 0.001, respectively). FGF19 amplifications, known to activate Wnt signalling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (p = 0.017). RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients.

  Study EGAS00001000604

• Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

  Background: The disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative of aggressive tumor behaviour and can thereby complement the prognostically favorable 1p/19q co-deletion. Results: Genome-wide, 50 base pair single-end, sequencing was performed to detect CNAs in a clinically well-characterized cohort of 98 formalin-fixed paraffin-embedded low-grade gliomas. CNAs are correlated with overall survival as an endpoint. Seventy-five additional samples from spatially distinct regions and paired recurrent tumors of the discovery cohort were analysed to interrogate the intratumoral heterogeneity and spatial evolution. Loss of 10q25.2-qter is a frequent subclonal event and significantly correlates with an unfavorable prognosis. A significant correlation is furthermore observed in a validation set of 126 and confirmation set of 184 patients. Loss of 10q25.2-qter arises in a longitudinal manner in paired recurrent tumor specimens, whereas the prognostically favorable 1p/ 19q co-deletion is the only CNA that is stable across spatial regions and recurrent tumors. Conclusions: CNAs in low-grade gliomas display extensive intratumoral heterogeneity. Distal loss of 10q is a late onset event and a marker for reduced overall survival in low-grade glioma patients. Intratumoral heterogeneity and higher frequencies of distal 10q loss in recurrences suggest this event is involved in outgrowth to the recurrent tumor.

  Study EGAS00001000643

• Clear cell sarcoma sequencing data

  This study shares DNA and RNA sequencing data from Clear cell sarcoma patients

  Study EGAS00001006072

• CD74-NRG1 fusions in lung adenocarcinoma

  We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-beta3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (p<0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.

  Study EGAS00001000653

• OAC RNASeq

  Please see our related publication, 'Molecular profiling to predict immunochemotherapy outcomes in esophageal adenocarcinoma'

  Study EGAS00001006468