8253 results for "canc*"

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• Genome-wide NanoRCS of cfDNA from plasma of healthy individuals

  Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant molecules, extremely sensitive sequencing methods are required. We adapted a new technique, NanoRCS, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule for genome-wide sequencing, and applied this to plasma of healthy controls.

  Study EGAS50000000695

• IL-27 promotes tumour control by enhancing cytotoxic T cell function

  Cytotoxic CD8+ T lymphocytes (CTL) are essential for anti-tumour immunity but are frequently dysfunctional in established tumours. Here, we show that expression of a CTL signature is strongly associated with IL-27 expression in diverse human and murine tumours. In mice, IL-27 acts directly on tumour-specific CTL to promote their persistence and effector function in the tumor microenvironment. Moreover, treatment with inducible IL-27 overexpression or a half-life-extended IL-27 protein in vivo is well tolerated, induces regression of large established tumours, drives an enhanced cytotoxic program in anti-tumour CTL, and synergizes with PD-L1 blockade. In cancer patients treated with anti-PD-1 or anti-PD-L1 therapy, high expression of IL-27 is associated with improved clinical response. Finally, IL-27 increases cytotoxicity and limits terminal differentiation of human CD8+ T cells during chronic antigen exposure. Our data demonstrate that endogenous IL-27 is essential for anti-tumour immunity and that IL-27 receptor agonism can safely improve anti-tumor T cell responses alone or in combination with PD-L1 blockade.

  Study EGAS50000000694

• Targeted pancancer RNA-Seq

  This dataset contains targeted RNA-Seq generated with the Illumina RNA Pan-Cancer panel. It comprises 2200 cancers from children and adults. The cancers represent a wide range of CNS, solid and haematopoeitic tumours. Samples are from pathology specimens including FFPE, fresh frozen, bone marrow aspirate and peripheral blood.The data is used for tumour driver identification. SNVs, indels and fusion detection.

  Study EGAS50000000700

• Characterization of stromal tumor-infiltrating lymphocytes and genomic alterations in metastatic lobular breast cancer

  Study EGAS00001004641

• RNA sequencing of follicular T cell lymphoma

  Study EGAS00001004646

• A comprehensive DNA methylation landscape of human and mouse cell lines derived from hematological malignancies

  Human cancer cell lines constitute useful models to study the primary disease and many relevant findings in tumor biology have been originated from them since the first immortalized cell line (HeLa) was obtained. The easy experimental intervention, the purity of the transformed cells and their versatility to undergo high-throughput screenings represent advantageous features of the established cancer cell lines. In recent years, major efforts have characterized in detail the multiomics make-up of hundreds of cancer cell lines and studied their association with sensitivity to anticancer drugs. Most of these studies have been genetic-centric and have not characterized in detail the epigenetic profiles underlying the characteristics of these cells or their impact on the efficacy of antitumoral compounds. In this regard, a past version of a DNA methylation microarray or a less accessible and more time-consuming such as reduced representation bisulfite sequencing have been used in those attempts to interrogate the epigenetic setting. Herein, we have obtained the DNA methylation profiles of 210 cell lines derived from hematological malignancies utilizing comprehensive DNA methylation microarrays that interrogates more than 850,000 and 285,000 CpG sites from human and mouse genomes, respectively. Importantly, we also provide a pharmacoepigenetic example of the potential use of this resource by showing how DNA methylation can predict response to nucleoside analogues.

  Study EGAS50000000627

• WES for CNV-verified CTCs enriched by high-throughout microfluidic device from entire cancer patient leukopak

  WES analysis (illumina platform, PE150, 100x coverage) was performed on a pool of copy number variation (CNV)-verified CTCs that were enriched using high-throughout microfluidic device from entire leukopak from patients with metastatic prostate cancer (GU-1 and GU-2).

  Study EGAS50000000724

• WGS of CTCs enriched using high-throughout microfluidic device from entire cancer patient leukopak

  Single-cell low-pass WGS analysis (illumina platform, PE150, 1-2x coverage) was performed on CTCs enriched using high-throughout microfluidic device from entire leukopak from patients with metastatic prostate cancer (GU-1 and GU-2) and metastatic hepatocellular carcinoma (HCC-1 and HCC-2).

  Study EGAS50000000723

• SAPCS Blood RNA-seq of prostate cancer patients

  The study aims to quantify the gene expression in blood samples in 20 prostate cancer patients under the Southern African Prostate Cancer Study (SAPCS). The objective is to identify a list of differentially expressed genes.

  Study EGAS50000000702

• Childhood B-cell acute lymphoblastic leukemia genomic and transcriptomic data

  The aim of the two studies was: 1) to genetically characterise childhood leukemia patients that lacked established cytogenetic abnormalities (termed B-other leukemia) and assess the clinical features of recurrent genetic abnormalities. 2) Assess the accuracy of whole genome sequencing as a diagnostic genetic test in childhood leukemia, relative to other traditional methods (karyotyping, FISH, MLPA) and whole transcriptome sequencing. As a result, this study includes targeted DNA-sequencing, whole genome sequencing and whole transcriptome sequencing data on childhood leukemia patients enrolled on UK clinical trials (UKALL2003 and UKALL2011).

  Study EGAS00001006863

• Molecular counting enables accurate and precise quantification of methylated ctDNA for tumor-naive cancer therapy response monitoring

  Personalized cancer treatment can significantly extend survival and improve quality of life for many patients, but accurate and real-time therapy response monitoring remains challenging. To overcome logistical and technical challenges associated with therapy response monitoring via imaging scans or assays that track the variant allele fraction (VAF) of somatic mutations in circulating tumor DNA (ctDNA), we developed a tumor-naive liquid biopsy assay that leverages Quantitative Counting Template (QCT) technology to accurately and precisely quantify methylated ctDNA (Northstar ResponseTM).

  Study EGAS50000000734

• Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes

  Head and neck squamous cell carcinoma (HNSCC) tumors were sampled from 88 patients. Samples were implanted subcutaenously into the flank of NOD/SCID/IL2R-/- mice. Mice were then monitored weekly for tumor growth and the time of initial palpation was recorded. Mice were euthanized when tumors reached 15 mm in diameter or after 6 months. If no tumor formed by 6 months, the patient tumor was defined as Non-engrafter (N). RNA-seq was performed on all primary tumor samples and successfully engrafted patient-derived xenograft (PDX) samples.

  Study EGAS50000000714

• Phase 1/2 Study of the Indoleamine 2,3-Dioxygenase 1 Inhibitor Linrodostat Mesylate Combined With Nivolumab or Nivolumab and Ipilimumab in Advanced Solid Tumors or Hematologic Malignancies

  Purpose: To evaluate the safety, efficacy, pharmacokinetics, pharmacodynamics, and biomarker data of linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies. Patients and Methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion], 100 or 200 mg) plus nivolumab (480 mg every [Q] 4 weeks [W] or 240 mg Q2W) or triplet therapy (part 3, linrodostat 20-100 mg QD; nivolumab 360 mg Q3W or 480 mg Q4W; ipilimumab 1 mg/kg Q6W or Q8W). Endpoints included safety and efficacy (co-primary; parts 2, 3), pharmacokinetics, pharmacodynamics, biomarkers, and efficacy (part 1). Results: Fifty-five, 494, and 41 patients were enrolled in parts 1, 2, and 3, respectively. Linrodostat exposures exceeded predicted therapeutic target concentrations starting at 50 mg. Rates of grade 3/4 adverse events were 50.1%-63.4%. The maximum tolerated linrodostat dose was 200 mg; dose-limiting toxicities were primarily immune related. Responses were observed across different cohorts, study parts, and tumor types, particularly in immunotherapy-naive patients. Kynurenine decreased with linrodostat + nivolumab, regardless of response. In contrast, interferon gamma (IFN-γ) gene expression signature was associated with response; in nonmelanoma patients, a composite of low tryptophan 2,3-dioxygenase (TDO2) gene expression plus high IFN-γ signature was associated with response. Conclusions: Linrodostat + nivolumab ± ipilimumab demonstrated a manageable safety profile. Kynurenine changes supported IDO1 pathway inhibition but did not correlate with response. A composite biomarker of low TDO2 expression plus high IFN-γ gene expression may predict response to linrodostat + nivolumab.

  Study EGAS50000000710

• FOCUS Trial

  We studied patients with advanced colorectal cancer, starting treatment with non-curative intent. 2135 unpretreated patients were randomly assigned to three treatment strategies in the ratio 1:1:1. Strategy A (control group) was single-agent fl uorouracil (given with levofolinate over 48 h every 2 weeks) until failure, then single-agent irinotecan. Strategy B was fl uorouracil until failure, then combination chemotherapy. Strategy C was combination chemotherapy from the outset.

  Study EGAS50000000725

• HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling

  Single-cell DNA-sequencing (scDNA-seq) enables decoding somatic cancer variation. Existing methods are hampered by low throughput or cannot be combined with transcriptome sequencing in the same cell. We propose HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a scalable yet simple and accessible assay to profile low-coverage DNA and RNA in thousands of cells in parallel. Our approach builds on a modification of the 10X Genomics platform for scATAC and multiome profiling. In applications to human cell models and primary tissue, we demonstrate the feasibility to detect rare clones and we combine the assay with combinatorial indexing to profile over 17,000 cells.

  Study EGAS50000000691

• Whole-exome sequencing profiling of patients with metastatic prostate cancer at VHIO

  Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and a RAD51 immunofluorescence (RAD51-IF) iprimary or metastatic biopsies from patients with stage IV prostate cancer. Whole-exome sequencing was pursued for paired tumor-normal samples.

  Study EGAS50000000736

• Epstein-Barr Virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review

  This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with especially the EBV-negative area showing more complex DNA aberrations, reminiscent of Chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlighting the impact of EBV loss on tumour behaviour.

  Study EGAS50000000706

• MET amplification in gastric cancer

  Targeting MET in gastric and gastroesophageal junction adenocarcinoma (GC) with monoclonal antibodies or tyrosine kinase inhibitors has had limited success. We hypothesize that other prognostic and response determining genetic alterations explain the poor outcome and lack of response to MET-targeted therapies.

  Study EGAS50000000744

• Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: CheckMate 649 biomarker analyses

  First-line nivolumab-plus-chemotherapy demonstrated superior overall survival (OS) versus chemotherapy for advanced gastroesophageal adenocarcinoma (CheckMate 649). Nivolumab-plus-ipilimumab provided durable responses and higher survival rates versus chemotherapy; however, the prespecified OS significance boundary was not met. To identify biomarkers predictive of differential efficacy outcomes, exploratory analyses were performed using whole-exome sequencing and RNA sequencing. Nivolumab-based therapies demonstrated improved efficacy versus chemotherapy in hypermutated and, to a lesser degree, Epstein Bar Virus-positive tumors compared with chromosomally unstable and genomically stable tumors. Within the KRAS-altered subgroup, only patients treated with nivolumab-plus-chemotherapy demonstrated improved OS benefit versus chemotherapy. Low stroma gene expression signature scores were associated with OS benefit with nivolumab-based regimens; high regulatory T-cell signatures were associated with OS benefit only with nivolumab-plus-ipilimumab. Our analyses suggest that distinct and overlapping pathways contribute to the efficacy of nivolumab-based regimens in gastroesophageal adenocarcinoma.

  Study EGAS50000000747

• An Integrated Approach to Patient Stratification and Therapy Selection in Acute Myeloid Leukemia

  Study EGAS00001004655

• Clinical relevance of TCGA subtypes for gastric cancer patients

  There is a clinical need for the availability of molecular biomarkers in the tratment of gastric cancer (GC), since survival rates remain poor with a 5-year survival rate of only ~`40% for patients with resectable disease. These markers will elad to a more tailored approach in the treatment of GC, which enhances efficacy and reduces toxicity. Recently, The Cancer Genome Atlas (TCGA) classified GC patients into four molecular subgroups: Epstein Barr Virus positive (EBV+), genomically stable (GS), microsatellite instable (MSI), and chromosomal instable (CIN). For this purpose we aim to collect tumor tissue blocks from patients who participated in the Dutch D1/D2 or the CRITICS trial and who gave informed consent for translational studies. Associations between TCGA subtypes and outcomes to these different therapeutic options will be analyzed.

  Study EGAS50000000779

• Development of a fully human glioblastoma-in-brain-spheroid model for accelerated translational research

  In glioblastoma (GBM) the intricate interplay between tumor cells and the surrounding microenvironment plays a crucial role in tumor progression, invasion, and therapeutic resistance. So far, studying these interactions in a controlled and representative model system has been challenging. Here, we report the development of hGliCS, a human glioma-cortical spheroid model that allows the elucidation of the biology of GBM cells and their interactions with a human-specific brain-like microenvironment and neurons. GBM cells efficiently invade the cortical spheroids, forming a well-connected network of communicating cells. The heterogeneous cellular states of the GBM cells within this model closely resembled findings previously observed in glioblastoma patients and in mouse xenografts. We observed a transition from predominantly mesenchymal-like cells to heterotopic states with a high diversity. In contrast to the substantial changes observed in the tumor cell population, the impact of the GBM cells on the neurons was minimal. We further demonstrate the suitability of hGliCS to test compounds targeting tumor-specific neurobiological features.

  Study EGAS50000000757

• A non-canonical lymphoblast in refractory childhood T-cell leukaemia

  Refractory cancers may arise either through the acquisition of resistance mechanisms by cancer cells or represent distinct diseases. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we performed single cell mRNA sequencing of T-ALL from children who did or did not respond to initial treatment. We identified a transcriptionally distinctive blast population, exhibiting features of innate-like lymphocytes, as the major source of refractory disease.

  Study EGAS50000000767

• Long-term Survival Update and Extended RAS Mutational Analysis of the CAIRO2 Trial: Addition of Cetuximab to CAPOX/Bevacizumab in Metastatic Colorectal Cancer

  Here we present updated survival of the CAIRO2 trial and assessed whether the addition of anti-EGFR to anti-VEGF therapy could still be an effective treatment option for patients with extended RAS/BRAF wildtype and left-sided metastatic colorectal cancer (mCRC).

  Study EGAS50000000775

• Pyjacker identifies enhancer hijacking events in acute myeloid leukemia including MNX1 activation via deletion 7q

  Acute myeloid leukemia with complex karyotype (ckAML) is characterized by high genomic complexity, including frequent TP53 mutations and chromothripsis. We hypothesized that the numerous genomic rearrangements could reposition active enhancers near proto-oncogenes, leading to their aberrant expression. We developed pyjacker, a computational tool for the detection of enhancer hijacking events, and applied it to a cohort of 39 ckAML samples. Pyjacker identified motor neuron and pancreas homeobox 1 (MNX1), a gene aberrantly expressed in 1.4% of AML patients, often as a result of del(7)(q22q36) associated with hijacking of a CDK6 enhancer. MNX1-activated cases show significant co-occurrence with BCOR mutations and a gene signature shared with t(7;12)(q36;p13) pediatric AML. We demonstrated that MNX1 is a dependency gene, as its knockdown in a xenograft model reduces leukemia cell fitness. In conclusion, enhancer hijacking is a frequent mechanism for oncogene activation in AML.

  Study EGAS50000000743