3391 results for "({!join from=dataset_studies to=id v=$q1}) OR ("cancer" OR "tumour" OR "tumor" OR "neoplasm" OR "malignant" OR "carcinoma" OR "metastase" OR "onco" OR "glioma" OR "leukaemia" OR "leukemia" OR "lymphoma")"

in 18.63 milliseconds.

• Single cell RNAseq data of human neurons, Bouwen et al Nat Comm 2025

  Brain tumor patients often suffer from epilepsy, but the underlying neuronal changes leading to this neurological symptom are not well understood. This study examined the transcriptomic profiles of human cortical neurons collected from brain tumor patients with or without seizures. The goals of the study were to identify the molecular identities of the recorded neurons and confirm that they are layer 2/3 pyramidal neurons rather than neuron-like tumor cells; and to compare the differential gene expression profiles between patients with and without epilepsy. For each patient, cortical neurons were rapidly isolated from surgically resected tissue and prepared using the Smart-seq2 protocol. Samples from 12 patients were sequenced on an Illumina HiSeq 2500 platform to generate their transcriptomic profiles.

  Study EGAS50000001369

• TRACERx 100: whole exome data of the first 100 TRACERx tumours

  BACKGROUNDTRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). METHODSMultiregion high-depth whole-exome sequencing (M-seq) was performed on 100 early stage NSCLC tumors resected prior to systemic therapy. A total of 327 tumor regions were sequenced and analyzed to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between ITH and recurrence-free survival (RFS). RESULTSWidespread ITH was observed for both somatic copy number alterations (median 48% [0.03-88%]) and mutations (median 30% [0.5-93%]). Driver mutations in EGFR, MET, BRAF and TP53 were almost always clonal. However, heterogeneous driver alterations occurring later in evolution were found in over 75% of tumors and were common in PIK3CA, NF1 and genes involved in chromatin modification and DNA response and repair. Genome doubling and ongoing dynamic chromosomal instability (CIN), illustrated by mirrored subclonal allelic imbalance, were identified as causes of ITH resulting in parallel evolution of driver copy number events, including amplifications of CDK4, FOXA1, and BCL11A. Elevated copy number heterogeneity was associated with shorter RFS (HR=4.9, P=0.00044), which remained significant in a multivariate analysis.CONCLUSIONSITH mediated through CIN, rather than point mutational heterogeneity, was associated with increased risk of relapse, supporting its value as a prognostic predictor, and the need to target this high-risk phenotype.

  Study EGAS00001002247

• Single-cell transcriptomic data from tumor samples

  Extramedullary multiple myeloma is an aggressive form of multiple myeloma where the myeloma cells escape BM microenvironment and infiltrate distant tissues.We analyse using single cell techniques, the composition and functional state of major immune cells in EMM tumor microenvironment, T and NK cells. This dataset contains the singlecell RNAseq data used in the publication. It includes scRNAseq data from tumor samples across extramedullary multiple myeloma soft tissue (EMM) (n=5; 3 additional samples in the study are under accession numbers mentioned in the publication), EMM bone marrow (EMM_BM) (n=5), and relapsed/refractory multiple myeloma (RRMM_BM) BM (n=6).

  Study EGAS50000001038

• RNAseq cutaneous and uveal melanoma liver metastases

  RNA sequencing analyses of tumor liver metastases from untreated cutaneous melanoma (CM) and uveal melanoma (UM) patients.

  Study EGAS00001004794

• Genomic Profiling of an anti-PD-L1 treated cohort of Newly Diagnosed GBM patients

  Checkpoint inhibitor therapy has limited efficacy in the outcomes of patients with glioblastoma (GBM). This study involves whole exome sequencing of newly diagnosed glioblastoma patients treated with concurrent atezolizumab, radiation therapy, and temozolomide. By analyzing 29 tumor-normal pairs, the study aims to explore the correlation between tumor genomics and the efficacy of PD-L1 blockade treatment outcomes and further identify which patients may benefit more from such therapy.

  Study EGAS50000000783

• WGS and WES of pediatric osteosarcoma

  Despite being the most common childhood bone tumor, the genomic characterization of osteosarcoma remains incomplete. Very few metastatic cases have been sequenced to date, a required step to better understand the progression and evolution of this tumor. Here, we present an integrative analysis of whole genome and whole exome sequencing (WGS and WES) of a cohort of primary and metastatic pediatric osteosarcoma, in order to identify recurrent genomic alterations between and within patients.

  Study EGAS00001003342

• Intratumor heterogeneity evaluation in primary HCC cells

  To investigate Intratumor heterogeneity in HCC and examine the effect of Intratumor heterogeneity on drug response, we collected fresh tissue from multiple tumor regions, representing the spatial extent and macroscopic heterogeneity of the primary tumors. Each region was subjected to primary culture (major part) and HE staining (minor part), the region contained more than 50% tumor cells was went on culture and examine by whole exome sequencing (WES) and CytoScan® HD Array.

  Study EGAS00001001135

• WES cutaneous and uveal melanoma liver metastases

  Whole exome sequencing analyses of tumor liver metastases from untreated cutaneous melanoma (CM) and uveal melanoma (UM) patients.

  Study EGAS00001004795

• Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting behavior

  Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), including the immune infiltrate. Here, we characterize the TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic and proteomic, including spatial single-cell approaches. Resolution of immune lineages indicates uniform high-infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoints, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M models tested. We show these myeloid populations communicate with H3-mutant cells mediating immunosuppression and sustaining tumor formation and maintenance. Dual inhibition of myeloid cells and immune checkpoints showed significant therapeutic benefit in pre-clinical syngeneic models. Our findings provide valuable characterization of the TME of oncohistone-mutant gliomas, and insights into means to modulate the myeloid infiltrate for the benefit of patients.

  Study EGAS00001007510

• scRNAseq - Notch Signaling Maintains a Progenitor-Like Subclass of Hepatocellular Carcinoma

  To clarify the cellular composition and the mechanism of efficacy following JAG1/NOTCH2 inhibition, we performed single-cell sequencing of LIV78 tumors isolated from control animals or following inhibition of JAG1 or NOTCH2. The results suggest that sensitive tumors consist of heterogeneous populations of cells in distinct transcriptional states and that Notch signals emerge from ligand-receptor co-expressing cells.

  Study EGAS50000000517

• Whole genome landscape of 25 metastatic cutaneous squamous cell carcinoma cSCC patients

  whole genome sequencing on lymph node metastases and blood DNA from 25 cSCC patients with regional metastases of the head and neck. We designed a multifaceted computational analysis at the whole genome level to provide a more comprehensive perspective of the genomic landscape of metastatic cSCC. This study contains the majority of 15 samples which are previously submitted in EGAC00001001100.

  Study EGAS00001006378

• ctDNA to predict risk of progression and death after trifluridin/tipiracil therapy

  Background. Late-line treatment in metastatic colorectal cancer (mCRC) can improve the prognosis. However, not every patient has a benefit and may experience severe side effects. Thus, predictive/prognostic biomarkers are urgently needed. Despite many promising results, the role of circulating tumor DNA (ctDNA) analysis in trifluridin/tipiracil (FTD/TPI) treated mCRC patients is so far still elusive. Study design. This prospective non-interventional translational biomarker phase II study enrolled 30 metastatic CRC patients treated with FTD/TPI. The primary study aim was to identify a molecular biomarker to predict overall survival (OS) benefit upon FTD/TPI treatment. Methods. mCRC patients (60% male, 40% female) with FTD/TPI therapy were included. Molecular profiling in cell-free DNA from plasma was performed prior to treatment and on average 4, 8 and 12 weeks after FTD/TPI initiation. Tumor levels were assessed as the highest variant allele frequency (hVAF) and correlated with OS. Uni- and multivariate analyses for survival were performed with clinical variables. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and ECOG performance status. Results. Compared to previous data, our disease control rate of 30% was lower with a median OS of 8.1 months and a median PFS of 3.2 months. At baseline (BL) and the first two follow-ups (FU), a hVAF cut-off of 7.5% was most discriminative (BL HR 0.39 95% CI 0.16 - 0.98 P=0.0212, FU1 HR 0.30 95% CI 0.12 -0.77 P=0.0021, FU2 HR 0.23 95% CI 0.08-0.70 P=0.0004) whereas at the last follow-up the stratification was most pronounced at a 15% cut-off. An elevated hVAF trajectory over time was associated with a higher risk of death. Conclusion. ctDNA is detectable in a high proportion of mCRC patients. Changes in ctDNA levels are associated with survival among FTD/TPI therapy and may identify patients who benefit most from treatment in these late-stage disease.

  Study EGAS00001006883

• MBD4 targeted sequencing

  We sequenced a gene of interest, MBD4, in both germline (n=1099) and tumor (n=192) sample from Uveal Melanoma patients.

  Study EGAS00001005012

• Whole exome sequencing of 12 NSCLC samples from 4 patients at MDACC

  Multi-region WES from 4 NSCLC patients, totaling 12 tumor samples and 4 matched control samples.

  Study EGAS00001005829

• IMCISION RNAseq

  RNA sequencing could be performed on all 32 baseline and 30 on-treatment primary tumor biopsies. Based on gene-set enrichment analysis, the epithelial to mesenchymal transition signature was enriched in baseline tumors of patients without MPR, though its expression was insufficient to predict ICB response. Baseline and on-treatment IFNγ and T-cell signature expression (Z-score) were not significantly higher in patients with an MPR.­­­ Baseline primary tumor hypoxia-associated gene expression in IMCISION did not predict ICB response. However, on-treatment biopsies of MPR tumor samples showed significantly lower hypoxia gene expression when compared to non-MPR samples. Moreover, in a paired analysis of baseline and corresponding on-treatment samples, a significant decrease of hypoxia-related gene expression was observed in MPR biopsies, while this decrease was absent in non-MPR biopsies.

  Study EGAS00001005454

• Non-Mendalian inheritance of extrachromosal DNA elements can drive disease evolution in glioblastoma

  Genomic heterogeneity of glioblastoma (GBM) is suspected to contribute to the poor response to therapy of this disease. We compared molecular characteristics between primary GBM, neurospheres and orthotopic xenograft models derived from the same parental tumor. Driver alterations were in majority propagated from tumor to model systems. Extrachromosomal amplifications of MET, a proto-oncogene coding for a receptor tyrosine kinase, were detected in three primary GBM, largely discarded in neurospheres cultures, but resurfaced in xenografts. The clonal dynamics inferred by somatic single nucleotide variants (sSNVs) in MET-amplified samples diverged from the pattern delineated by the MET amplification event suggesting that the MET event and sSNVs were inherited in different manners. Our analysis shows that extrachromosomal elements are able to drive tumor progression.

  Study EGAS00001001878

• Prediction of homologous recombination deficiency identifies colorectal tumors sensitive to PARP inhibition

  BRCAness is a well-established feature in breast, ovarian, prostate and pancreatic carcinomas, our recent findings indicate that up to 15% of colorectal cancers (CRC) also harbor defects in the HR pathway, presenting promising opportunities for innovative therapeutic strategies in CRC patients. We developed a new tool called HRDirect, which builds upon the HRDetect algorithm and is able to predict HRD from reference-free tumor samples. We validated HRDirect using matched breast cancer and CRC patient samples. Subsequently, we assessed its efficacy in predicting response to the PARP inhibitor olaparib by comparing it with two other commercial assays: AmoyDx HRD by Amoy Diagnostics and the TruSight Oncology (TSO) _500 HRD panel by Illumina NGS technology. While all three approaches successfully identified the most PARPi-sensitive CRC models, HRDirect demonstrated superior precision in distinguishing resistant models compared to AmoyDX and TSO500-HRD, which exhibited overlapping scores between sensitive and resistant cells. Furthermore, we propose integrating HRDirect scoring with ATM immunohistochemical analysis as part of our "composite biomarker approach" to enhance the identification of HRD tumors, with an immediate translational and clinical impact for CRC personalized treatment.

  Study EGAS50000000426

• Vaccine-Expanded Plasmablast-like B Cells Are Associated with Response to Dendritic Cell Therapy in Metastatic Melanoma

  Dendritic cells (DCs), either monocyte-derived (moDCs) or naturally circulating, have been employed in cancer treatment across both metastatic and adjuvant settings. DC vaccines (DC Vax) are capable of inducing tumor-specific immune responses, yet clinical outcomes have thus far fallen short of expectations. Here, we performed a multi-omics analysis of the apheresis product, including CD14⁺ monocytes, and the final DCVax formulation. Among all the components analyzed, the most striking finding was the unexpected presence of CD19⁺ B cells within the DC Vax formulation, which distinguished Responders from Non-Responders to moDC vaccination in metastatic melanoma. The abundance of B cells in DC Vax correlated with their peripheral frequency; however, within the vaccine, these cells acquired a CD20lowCD27hiCD38hi plasmablast-like phenotype, distinct from their autologous circulating B-cell precursors. Notably, a parallel observation was made in Responders, whose pre-treatment lesions were enriched in B cells organized as Tertiary Lymphoid Structures. These results underscore the importance of B cells in both baseline immunity and DCVax formulation, hinting at unexplored mechanisms by which they may influence vaccine effectiveness.

  Study EGAS50000001177

• Whole genome sequencing of Ewings Sarcoma

  Sarcomas are cancers of the bone and soft tissue often defined by their gene fusions. However, the timing, context, and processes by which these pathogenic fusions arise are unknown. We explored this in Ewing sarcoma, a cancer driven by EWSR1-ETS fusions, with very few cooperating mutations. Combining whole-genome sequencing with enhanced informatics, we found that the EWSR1-ETS fusion arose from striking rearrangement clusters in 42% of cases (52/124). Notably, these were organized in loops that universally contained the fusion at their center, while also weaving up to 18 genes together with it. We found the same pattern of rearrangements in three additional types of sarcoma. From these data, we define a new signature for sarcoma fusions that precedes other somatic changes, in the earliest replicating DNA of the genome. This dramatic, sudden process impinges on many genes – generating multiple coding changes that profoundly affect the transcriptome, with the disease-defining gene fusion at its core. These rearrangement loops emerge in an early ES clone from which both the primary tumor and the lethal relapse emerged, and then evolved in parallel until clinically detected.

  Study EGAS00001003385

• Ewings Sarcoma RNA-Seq

  Sarcomas are cancers of the bone and soft tissue often defined by their gene fusions. However, the timing, context, and processes by which these pathogenic fusions arise are unknown. We explored this in Ewing sarcoma, a cancer driven by EWSR1-ETS fusions, with very few cooperating mutations. Combining whole-genome sequencing with enhanced informatics, we found that the EWSR1-ETS fusion arose from striking rearrangement clusters in 42% of cases (52/124). Notably, these were organized in loops that universally contained the fusion at their center, while also weaving up to 18 genes together with it. We found the same pattern of rearrangements in three additional types of sarcoma. From these data, we define a new signature for sarcoma fusions that precedes other somatic changes, in the earliest replicating DNA of the genome. This dramatic, sudden process impinges on many genes – generating multiple coding changes that profoundly affect the transcriptome, with the disease-defining gene fusion at its core. These rearrangement loops emerge in an early ES clone from which both the primary tumor and the lethal relapse emerged, and then evolved in parallel until clinically detected.

  Study EGAS00001003062

• SS18-SSX-mediated hijacking of BAF complexes drives synovial sarcoma

  Synovial sarcoma (SS) is defined by a recurrent t(x;18) chromosomal translocation, which produces the hallmark SS18-SSX oncogenic fusion. Incorporation of SS18-SSX into BAF complexes renders BAF complexes aberrant in two distinct manners: the addition of 78aa of SSX onto SS18, and concomitant loss of BAF47 assembly. However, the importance and functional contributions of each of these perturbations on BAF complex targeting and gene expression regulation remain unclear. Here we use an integrative set of genomic approaches in human cancer cell lines and primary tumor samples to define the mechanistic consequences of the SS18-SSX fusion oncoprotein. We find that SS18-SSX hijacks BAF complexes to broad polycomb domains to activate bivalent genes, driving a unique gene expression program distinct from other loss-of-function BAF complex malignancies. Importantly, restoration of BAF47 rescues enhancer activation but is dispensable for proliferative arrest in cell lines. These results demonstrate that gain-of-function SS18-SSX-mediated BAF complex targeting and gene activation is the driving event in SS, and present a mechanism by which distinct functions of BAF complexes can be co-opted to drive oncogenesis.

  Study EGAS00001002920

• Dynamics of checkpoint receptors in γδ T cell subsets are associated with clinical responses during anti-PD-1 immunotherapies

  Gamma delta (γδ) T cells are innate-like lymphocytes with potent anti-tumor properties. Herein, we show that immune checkpoint receptors (ICRs) display differential expression and regulation by the JAK-STAT pathway in Vδ1 and Vδ2 cells and identify constitutive (e.g. TIGIT, PD-1) and inducible (e.g. TIM-3, LAG-3, CTLA-4) ICRs. In melanoma, all γδ T cell subsets downregulated AP-1 transcription factors, but Vδ1 cells specifically expressed high levels of ICR, TOX and inhibitory killer Ig-like receptor (KIR) transcripts, reminiscent of exhaustion. However, patient-derived cells were functionally competent, although induction of LAG-3 and CTLA-4 was impaired. During anti-PD-1 monotherapy, Vδ1 cells specifically bound high levels of therapeutic antibody but only in patients who responded to treatment, revealing a potential new prognostic marker for evaluating the efficacy of IC blockade (ICB) therapy. Finally, expression of KIR genes in Vδ1 cells was downregulated in response to successful ICB therapy. Collectively, our data indicate an intricate relationship between ICRs and γδ T cells and reveal novel approaches by which these cells can be harnessed in order to discern or improve cancer immunotherapy.

  Study EGAS50000001270

• Infant Glioma Molecular Subtype

  Infant gliomas have completely different clinical behavior than gliomas in children and adults. Low-grade tumors are more aggressive with a higher mortality rate, while high-grade tumors are more benign. However, we have little understanding of their biology and so cannot explain this behavior and what constitutes optimal clinical management. To solve this enigma, we performed a comprehensive genetic analysis of the largest cohort to date of infantile gliomas. We uncovered several important findings which dramatically change the management of these cancers. Infant hemispheric gliomas harbor unique alterations in ROS, ALK, MET and other genes found in adult carcinomas. Unlike in adults, they are typically the only alteration present and some of these tumors regress from high- to low-grade partially explaining their favorable clinical outcome. Midline gliomas harbor RAS/MAPK pathway mutations, progress rapidly, and do not respond to current chemoradiation approaches, partially explaining their poorer outcome. These data suggest that infant gliomas require different therapeutic approaches including early use of targeted therapies.

  Study EGAS00001003714

• Methylome profiling of Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) and a patient derived cell-line model

  Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1 using the twist human methylome panel.

  Study EGAS50000000026

• Ultra-fast deep-learned pediatric CNS tumor classification.

  The primary treatment of CNS tumors starts with a neurosurgical resection in order to obtain tumor tissue for diagnosis and to reduce tumor load and mass effect. The neurosurgeon has to decide between radical resection versus a more conservative strategy to prevent surgical morbidity. The prognostic impact of a radical resection varies between tumor types. However due to a lack of pre-operative tissue-based diagnostics, limited knowledge of the precise tumor type is available at the time of surgery. Current standard practice includes preoperative imaging and intraoperative histological analysis, but these are not always conclusive. After surgery, histopathological and molecular tests are performed to diagnose the precise tumor type. The results may indicate that an additional surgery is needed or that the initial surgery could have been less radical. Using rapid Nanopore sequencing, a sparse methylation profile can be directly obtained during surgery, making it ideally suited to enable intraoperative diagnostics. We developed a state-of-the-art neural-network approach called Sturgeon, to deliver trained models that are lightweight and universally applicable across patients and sequencing depths. We demonstrate our method to be accurate and fast enough to provide a correct diagnosis with as little as 20 to 40 minutes of sequencing data in 45 out of 49 pediatric samples, and inconclusive results in the other four. In four intraoperative cases we achieved a turnaround time of 60-90 minutes from sample biopsy to result; well in time to impact surgical decision making. We conclude that machine-learned diagnosis based on intraoperative sequencing can assist neurosurgical decision making, allowing neurological comorbidity to be avoided or preventing additional surgeries.

  Study EGAS00001007475