4957 results for "*oma"

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• Neoadjuvant combination PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable urothelial carcinoma

  Immune checkpoint therapy (ICT) is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma (UC), with one study reporting data in cisplatin-ineligible patients who received anti PD-L1 monotherapy. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathologic complete response (pCR) rate of 17%. Here, we report on the first pilot combination neoadjuvant trial (NCT02812420) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high risk features (N=28). Primary endpoint was safety and we observed 6 of 28 patients (21%) with grade ≥3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (N=4), hepatitis and colitis (N=2). We also observed pCR of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (N=24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized UC, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment. Publication: Gao et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nature Medicine volume 26, pages1845–1851(2020)

  Study EGAS00001004074

• Analysis_of_resistance_to_PLX4032

  We have collected material from a patient who had BrafV600E mutant melanoma that wastreated with PLX4032. We have germline DNA from the patient and DNA and RNA fromdistinct lesions before and after treatment with PLX4032. We would like to exome sequencethese samples to gain a snap shot of the mechanisms of resistance that are operative.

  Study EGAS00001000415

• Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma

  Neuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.

  Study EGAS00001007650

• Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers

  Purpose: Shallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities. Experimental Design: sWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs. CN alterations, mutational data and CN signatures were derived, and associations to clinicopathologic and outcomes data were assessed. Results: In 187 p53abn ECs, 5 distinct CN signatures were identified. Signature 5 was associated with BRCA1/2 CN loss with features similar to HGSOC HRD signature. 22% potential HRD cases were identified, 35 patients with signature 5, and 8 patients with BRCA1/2 somatic mutations. Signatures 3 and 4 were associated with whole genome duplication, and CCNE1, ERBB2 and MYC amplifications, with mutations in PIK3CA enriched in signature 3. We observed improved overall survival (OS) for patients with signature 2 and worse OS for signatures 1 and 3. 28% of patients had CCNE1 amplification and this subset was enriched with carcinosarcoma histotype. 34% of patients, across all histotypes, had ERBB2 amplification and/or HER2 overexpression on immunohistochemistry, which was associated with worse outcomes. Mutations in PPP2R1A (29%) and FBXW7 (16%) were among the top 5 most common mutations. Conclusions: sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.

  Study EGAS00001007661

• RNAseq on 20 samples of multiple myeloma patients and 3 normal plasma cells.

  RNAseq was performed using 200 ng of total RNA by GATC Biotech. Directional libraries were performed after mRNA selection by polyA selection using UTP method. RNA-seq libraries were sequenced on HiSeq2500 Illumina machine using 100bp paired-end reads. Reads alignment was performed using the STAR aligner (version 2.4.0f1) and human genome hg19 as reference.

  Study EGAS00001004347

• Longitudinal Single-cell Genomic Analysis of Initial and Recurrent Meningioma

  This study investigates the genomic evolution of meningioma through single-cell whole genome sequencing analysis of paired tumor samples. We analyzed tumor tissues from initial and recurrent meningiomas from the same patients to understand clonal evolution and tumor progression. The research aims to characterize copy number alterations and genomic heterogeneity at single-cell resolution across different time points of tumor development.

  Study EGAS50000000860

• metastatic uveal melanoma tumour biopsies

  Tumour biopsies were obtained from uveal melanoma patients pre and 16 days post treatment with tebentafusp. Biopsies, which were either snap frozen or put in RNA later, were analysed by bulk RNA sequencing (50 million reads per sample) using the Illumina NovaSeq system.

  Study EGAS50000000864

• Primary Neuroblastoma Circle-seq

  We generated Circle-seq data for primary neuroblastoma to describe the landscape of extrachromosomal circular DNA in neuroblastoma.

  Study EGAS00001004797

• Clonal hematopoiesis in metastatic urothelial and renal cell carcinoma

  This study aimed to determine the prevalence and clinical relevance of clonal hematopoiesis in metastatic urothelial and renal cell carcinoma.

  Study EGAS50000000870

• A Comprehensive Genetic Study of Classical Hodgkin Lymphoma Using Circulating Tumour DNA

  This study on classical Hodgkin lymphoma (cHL) used advanced methods to analyse circulating tumour DNA (ctDNA) in 297 cases, offering insights into its genetic landscape and linking it to disease pathophysiology and clinical progression. Key findings include the identification of whole genome duplication as a predictor of poor chemotherapy response. Additionally, a highly recurrent somatic expression quantitative trait locus of the BCL6 gene was discovered, implicating regulatory mutations in cHL pathophysiology and highlighting BCL6 as both a vulnerability and therapeutic target. Consensus clustering identified two cHL subtypes distinguished by the underlying mechanisms of genetic instability, rather than by specific genetic mutations or EBV infection. The study also linked the number and clonality of neoantigens with tumour microenvironment and response to checkpoint blockade. Finally, our results suggested ctDNA analysis as a tool to distinguish ambiguous PET/CT-positive lesions persisting after treatment, aiming to reduce unnecessary medical interventions.

  Study EGAS50000000873