4055 results for "*oma"

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• Tumor Profiler Project - MEL bulk transcriptomics data

  The dataset contains bulk transcriptomics data from 80 samples from 77 different patients with melanoma. Samples were collected from the tumor. Sequencing was performed in paired-end mode and sequencing data is provided in fastq format.

  Dataset EGAD50000000851

• Tumor Profiler Project - MEL scDNA data

  The dataset contains 10x Chromium single-cell DNA sequencing data from 63 samples from 60 different patients with melanoma. Samples were collected from the tumor. Sequencing was performed in paired-end mode and sequencing data is provided in fastq format.

  Dataset EGAD50000000852

• Tumor Profiler Melanoma Study

  The Tumor Profiler Study is an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease. Technologies used are digital pathology, targeted NGS, single-cell RNA, single-cell DNA, bulk RNA, bulk proteotyping, single-cell CyTOF, imaging mass cytometry, pharmacoscopy, 4i Drug Response Profiling, and cell-free DNA. These technologies were applied to 240 tumor samples collected over 3 years across three cancer indications: metastatic melanoma, metastatic epithelial ovarian cancer, and acute myeloid leukemia (AML). Here, we publish the scRNA, scDNA, and bkRNA data of the melanoma cohort.

  Study EGAS50000000599

• Tumor Profiler Project - MEL scRNA data

  The dataset contains 10x Chromium single-cell transcriptomics data from 65 samples from 62 different patients with melanoma. Samples were collected from the tumor. Sequencing was performed in paired-end mode and sequencing data is provided in fastq format.

  Dataset EGAD50000000853

• High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells

  Neoantigen-specific T cell receptors (neoTCRs) promise safe, personalized anti-tumor immunotherapy. Previously, we identified diverse neoTCRs restricted to different neoantigens in a melanoma patient. In this work, we now combined single-cell TCR- and RNA-sequencing after neoantigen-specific restimulation of peripheral blood-derived CD8+ T cells of this patient. We detected novel neoTCRs with specificity to the previously detected neoantigens and observe a heterogeneous spectrum of TCR-intrinsic activation patterns in response to a shared neoepitope ranging from previously detected higher frequent neoTCRs with moderate activation to rare ones with initially stronger activation.

  Study EGAS50000000600

• scRNA/TCR-seq of CD8+ T cells from a melanoma patient

  Specific in vitro stimulation of patient-derived PBMC with the neoantigens SYTL4-S363F and KIF2C-P13L was followed by enriching for CD137+ activated T cells. Restimulated T cells as well as an unstimulated patient PBMC sample from the same time point were used for scRNA-Seq/scTCR-Seq.

  Dataset EGAD50000000854

• Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups

  Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. In summary, Pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.

  Study EGAS00001006402

• Single-cell RNA-seq of peripheral blood mononuclear cells in classic Hodgkin lymphoma

  Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.

  Study EGAS00001007569

• Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome

  Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP.  This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported.

  Study EGAS00001007937

• Pilocytic Astrocytoma RNA sequencing

  This dataset contains RNA sequencing samples from the Duesseldorf/LIsbon pilocytic astrocytoma cohort which was profiled using Proteogenomics (RNA Sequencing, proteomics and methylation). There are 48 samples which were sequenced using paired-end sequencing at the University Hopstial Dusseldorf.

  Dataset EGAD00001009053

• Single-cell RNA-seq of peripheral blood mononuclear cells in classic Hodgkin lymphoma

  Abstract: Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.

  Dataset EGAD00001011360

• Dataset for EGAS00001007937

  WGS, RNAseq, Methylation, variant calling analysis for a Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome

  Dataset EGAD00001015412

• Mutational_burden_in_human_hair_follicles

  We would like to dissect human hair follicles and assess the mutations found in diffferent parts of the follicle eg bulge, root etc. We can also compare this with mutations found in the surrounding epidermis of the same patients (this is done under a different study). This may provide insights into the origin of PTCH1 mutants frequently seen in basal cell carcinoma but so far not located in our whole epidermis work as well as defining the clonality of the hair follicle

  Study EGAS00001004462

• Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated

  The transcription factor FOXR2 is the universal driver of childhood central nervous system neuroblastoma, FOXR2 activated (NB-FOXR2). NB-FOXR2 tumors arise exclusively in the brain hemispheres, and despite morphological similarities to other pediatric brain tumors, they are a molecularly distinct entity based on DNA methylation profiling. The cell-of-origin is unknown. Here, we profiled a cohort of rare NB-FOXR2 tumors by bulk and single-cell transcriptomics. Through systematic comparative analyses, we delineate tumor transcriptional states and candidate cell-of-origin. More broadly, we demonstrate systematic molecular profiling of childhood cancers to orient oncogenic targeting for in vivo modeling, a critical resource for the study of rare tumors and development of therapeutics.

  Study EGAS00001007247

• Human tumor single-cell mutiome

  We profiled 1 patient neuroblastoma-FOXR2 tumor sample by single-cell multiome RNA + ATAC. The raw fastqs are provided.

  Dataset EGAD00001010902

• Human tumor single-nuclei RNA-seq

  We profiled 4 patient neuroblastoma-FORX2 tumor samples by single-nuclei RNA-seq using 10X Chromium 3'. The raw fastqs are provided.

  Dataset EGAD00001010903

• Ewing and Ewing-like-sarcoma tumoroid biobank reveals distinct drug sensitivities: translocation makes the difference

  Ewing sarcoma (ES) and Ewing-like sarcomas (ELS) are highly aggressive tumors found in soft tissues and bone of mostly children and young adults. Despite being different in many aspects, including genetics, possible cell-of-origin, and pathology, patients with any of these entities all receive the same therapeutic regimen. Currently, there is a lack of preclinical cell models that can predict drug response of these entities in vitro. Here, we describe a pediatric ES and ELS tumor organoid (tumoroid) biobank containing tumoroids with different translocations, including EWSR1::FLI1, EWSR1::ERG, CIC::DUX4, and BCOR-rearrangements. Using histology, whole genome sequencing and RNA sequencing, we demonstrate that these tumoroids retain key properties of their matching patient tumors. In addition, we traced tumor subclones in the tumoroids across patient-matched longitudinal samples, which showed that cellular heterogeneity was maintained. We subsequently performed drug screening on the tumoroid models, which unveiled entity-specific drug sensitivity to various cytotoxic compounds and targeted compounds, including MCL-1 inhibitors for CIC::DUX4 sarcomas. Taken together, this newly established ES and ELS patient-derived tumoroid biobank generates a unique source of material for future basic cancer research and drug-screening.

  Study EGAS00001007941

• Human tumor bulk RNA-seq

  We profiled 7 patient neuroblastoma-FOXR2 tumor samples by bulk RNA-seq. The raw fastqs are provided.

  Dataset EGAD00001010901

• RNA-seq dataset of Ewing and Ewing-like-sarcoma tumoroid biobank reveals distinct drug sensitivities: translocation makes the difference

  Creation of living organoid biobank for ewing and ewing-like sarcomas

  Dataset EGAD00001015419

• WXS dataset of Ewing and Ewing-like-sarcoma tumoroid biobank reveals distinct drug sensitivities: translocation makes the difference

  Creation of living organoid biobank for ewing and ewing-like sarcomas

  Dataset EGAD00001015417

• WGS dataset of Ewing and Ewing-like-sarcoma tumoroid biobank reveals distinct drug sensitivities: translocation makes the difference

  Creation of living organoid biobank for ewing and ewing-like sarcomas

  Dataset EGAD00001015418

• Genomic Profiling of Pediatric Tumors by Cell Free DNA Sequencing

  BACKGROUND Analysis of cell-free DNA (cfDNA) from peripheral blood has been studied extensively for detection and monitoring therapy response in adult cancers, but utility in pediatric tumors is unclear. METHODS We studied 233 children with hematologic, solid and brain tumors. cfDNA was extracted from 1 mL of plasma collected at diagnosis. Circulating tumor DNA (ctDNA) in cfDNA was quantified and diverse classes of somatic genomic variants were detected using PeCan-Seq. PeCan-Seq findings were compared with matched tumor whole-genome and whole-exome sequencing data. Minimal residual disease (MRD) status was evaluated by cfDNA PeCan-Seq in 14 patients with B-cell acute lymphoblastic leukemia. RESULTS Plasma cfDNA yields at diagnosis were higher for hematologic malignancies than for solid and brain tumors. Patients with hematologic malignancy were 100% ctDNA-positive, the median ctDNA fraction in cfDNA was 0.77. We detected 97% variants that were present in tumors and covered by the capture panel, and 50 subclonal variants that were present in cfDNA only. Our approach enabled detection of sequence and structural variants in B-ALL ctDNA at varying levels of MRD. Nineteen of 38 patients with solid tumors were ctDNA-positive, with high prevalence in Ewing Sarcoma, liver tumors and osteosarcoma. One of 19 brain tumor patients was ct-DNA positive, indicating lack of utility for plasma-derived cfDNA in this disease. Notably, cfDNA analysis of a single plasma sample identified genomic features in ctDNA derived from B-ALL, concurrent primary neuroblastoma, and a later neuroblastoma relapse, indicating that genomic variations from multiple tumors could be detected simultaneously. CONCLUSIONS Pediatric patients with hematologic malignancy had an abundance of plasma ctDNA at diagnosis. Plasma ctDNA levels varied between different solid tumor types, more studies are needed to determine utility. Panel-based cfDNA sequencing could serve as a non-invasive approach for pediatric cancer diagnosis and disease monitoring.

  Study EGAS50000000072

• Orthotopic Patient-Derived Xenografts of Pediatric Solid Tumors

  Pediatric solid tumors arise from endodermal, ectodermal, or mesodermal lineages. Although the overall survival of children with solid tumors is 75%-80%, that of children with recurrent disease is below 30%. To capture the complexity and diversity of pediatric solid tumors and establish new models of recurrent disease, we developed a protocol to produce orthotopic patient-derived xenografts (O-PDXs) at diagnosis, recurrence, and autopsy. Tumor specimens were received from 168 patients, and 64 O-PDXs were established for 12 types of pediatric solid tumors. The origins of the O-PDX tumors were reflected in their gene-expression profiles and epigenomes. Genomic profiling of the tumors, including detailed clonal analysis, was performed to determine whether the clonal population in the xenograft recapitulated the patient’s tumor. We identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma O-PDX tumors in vivo.

  Study EGAS00001002528

• Comprehensive genomic profiling of matched glioblastoma tumours, cell-lines, and xenografts reveals genomic stability and adaptation to disparate growth environments

  The mandate of this project was to use drug screening to deliver new drugs for glioblastoma (GBM) to clinical trials, and perform genomic assessment of GBM to discover new therapeutic targets and predictors of response. The sequencing data in this set was derived from GBM patient tumor samples, matched brain tumor initiating cells lines (BTICs), and tumor tissue derived from orthotopic implants.

  Study EGAS00001002709

• Ultra-sensitive ctDNA monitoring required for predicting response and resistance to immunotherapy in advanced melanoma

  Circulating tumor DNA (ctDNA) monitoring in peripheral blood has shown promise for disease surveillance and prognostication of ICI response. Yet even in the metastatic context, ctDNA signals can be missed, suggesting the need for increased assay sensitivity. We used a tumor-informed ctDNA assay capable of detection down to 1 part-per-million (PPM) ctDNA to profile 188 plasma samples from 23 melanoma patients receiving ICI over several years. Residual disease was detected in ctDNA over a broad range, from 130,000 PPM down to 2.3 PPM, with approximately a quarter of detections below 50 PPM. Early on-treatment increases in ctDNA level, and both ctDNA-based molecular clearance (mCR) and molecular progression (mPD) were all prognostic of both OS and PFS. Additionally, mCR consistently preceded radiographic imaging. Our results show the importance and utility of an ultra-sensitive ctDNA assay in advanced melanoma treated by ICI with potential implications for other cancers.

  Study EGAS50000000550

• WGS from melanoma patient tumor/normal pairs and longitudinal panel-based cfDNA sequencing data

  This data includes paired WGS from tumor/normal and longitudinal panel-based sequencing data of plasma-derived cfDNA from melanoma patients being treated with ICI.

  Dataset EGAD50000000785

• RNA sequencing of Ewing and CIC-DUX4 sarcoma tumoroid models

  Tumoroid models from Ewing sarcoma and CIC-DUX4 sarcoma models were generated from patient tumor biopsies. Tumoroids were established in 3D matrigel domes and then propagated on a matrige layer. RNA sequencing was performed with established tumoroid models.

  Study EGAS50000000380

• Whole exome sequencing of Ewing sarcoma and CIC-DUX4 sarcoma

  Whole exome sequencing of a collection of 6 Ewing sarcoma and 3 CIC-DUX4 sarcoma tumoroids plus 4 matched patient tumors and normal tissue. Tumoroids were established from digested patient tumor material as 3D culture in Matrigel. After 2-3 month of growth, Genomic DNA was isolated from individual tumoroid models using the DNeasy Blood & Tissue Kit (Qiagen) and used for whole exome sequencing. Genomic DNA from corresponding patient tumors and matched normal tissue was tested in parallel, if available.

  Dataset EGAD50000000556

• RNA sequencing of Ewing sarcoma and CIC-DUX4 sarcoma

  RNA sequencing of a collection of 6 Ewing sarcoma and 3 CIC-DUX4 sarcoma tumoroids plus 3 matched patient tumors. Tumoroids were established from digested patient tumor material as 3D culture in Matrigel. After 2-3 month of growth, RNA was isolated from individual tumoroid models using the RNeasy Kit (Qiagen) and used for whole exome sequencing. RNA from corresponding patient tumors was tested in parallel, if available.

  Dataset EGAD50000000557

• University Children`s Hospital Sarcoma Research

  Dac EGAC50000000260

• Whole exome sequencing of Ewing and CIC-DUX4 sarcoma tumoroid models

  Tumoroid models from Ewing sarcoma and CIC-DUX4 sarcoma models were generated from patient tumor biopsies. Tumoroids were established in 3D matrigel domes and then propagated on a matrige layer. Whole exome sequencing was performed with established tumoroid models.

  Study EGAS50000000379

• Diversity of the immune microenvironment and response to checkpoint inhibitor immunotherapy in mucosal melanoma

  Mucosal melanoma (MucM) is a rare cancer with a poor prognosis and low response rate to immune checkpoint inhibition (ICI) compared to cutaneous melanoma (CM). To explore the immune microenvironment and potential drivers of MucM’s relative resistance to ICI drugs, we characterized 101 MucM tumors (43 head and neck, 31 female urogenital, 13 male urogenital, 11 anorectal, and 3 other gastro-intestinal) using bulk RNA-sequencing (RNAseq). The original publication is written by JL Vos, JJH Traets, et al. and published in JCI Insight in 2024.

  Study EGAS50000000631

• Mucosal Melanoma transcriptomes

  This is an RNA sequencing dataset of 101 mucosal melanoma tumors. The original corresponding study is titled "Diversity of the immune microenvironment and response to checkpoint inhibitor immunotherapy in mucosal melanoma" by J.L. Vos et al., published in JCI Insight.

  Dataset EGAD50000000892

• Detection of clinically relevant genetic and transcriptomic landscape in DLBCL uniformly treated by R-CHOP

  Recent studies using next-generation sequencing strategies have described the landscape of genetic alterations in diffuse large B-cell lymphoma (DLBCL). However, little is known about the clinical relevance of recurrent mutations and copy number alterations and their transcriptional footprints. This study examines the frequency, interaction and clinical impact of recurrent genetic aberrations in DLBCL using high-resolution technologies in a large population-based cohort.

  Study EGAS00001002657

• Molecular profiling of metastatic uveal melanoma

  Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations were overrepresented and occurred in 29/32 of cases. An outlier tumor had high mutational burden associated with UV-damage. CDKN2A deletions also occurred, which are rarely present in primaries. We profiled recurrent copy number alterations associated with metastasis and performed a focused knockdown screen on overexpressed targets. We investigated the role of BAP1 by reintroducing a functional allele into a deficient patient-derived cell line, revealing a broad shift towards a transcriptomic subtype associated with better prognosis. Tumor-infiltrating lymphocytes were in several cases tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 was abundant. This study represents the largest whole-genome analysis of uveal melanoma to date and presents an updated view of the metastatic disease.

  Study EGAS00001004296

• Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity and Tumor-Immune Evolution in Refractory Mantle Cell Lymphoma

  The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that the molecular targeting of BIRC5/survivin, locates at 17q and upregulates in resistant MCL tumor cells, results in marked tumor inhibition in preclinical models. In addition, we discovere notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveales diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

  Study EGAS00001005019

• Epigenetic landscape reorganization and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma

  Accurate grading of IDH-mutant gliomas is crucial for determining patient prognosis and guiding treatment decisions. However, histological grading can be challenging, so we aimed to identify objective molecular markers. To this end, we conducted bulk RNA sequencing on primary IDH-mutant astrocytomas (n=138) from the prospective CATNON trial, which evaluated the prognostic impact of adjuvant and concurrent temozolomide. Using this data, we sought to identify molecular markers linked to increased malignancy in IDH-mutant astrocytomas to establish objective grading criteria.

  Study EGAS50000000381

• Single-cell RNA-seq data of the tumor microenvironment of lymphocyte-rich Hodgkin lymphoma and other Hodgkin lymphoma subtypes

  Lymphocyte-rich classic Hodgkin lymphoma (LR-CHL) is a rare subtype of Hodgkin lymphoma. Recent technical advances have allowed for the characterization of specific crosstalk mechanisms between malignant Hodgkin Reed-Sternberg (HRS) cells and different normal immune cells in the tumor microenvironment (TME) of CHL. However, the TME of LR-CHL has not yet been characterized at single cell resolution. Here, using single cell RNA sequencing, we examined the immune cell profile of 8 cell suspension samples of LR-CHL in comparison to 20 samples of the mixed cellularity (9 cases) and nodular sclerosis (11 cases) subtypes of CHL, as well as 5 reactive lymph node controls.

  Study EGAS00001005541

• Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies

  The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients. Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit.

  Study EGAS00001007585

• Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma

  Study EGAS00001000226

• 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

• 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

• Association of Age at Diagnosis and Genetic Mutations in Patients with Neuroblastoma

  Neuroblastoma is diagnosed over a wide age range from birth through young adulthood, and older age at diagnosis is associated with a decline in survivability. We performed whole genome sequencing of DNA from diagnostic tumors and their matched germlines from 40 patients with metastatic neuroblastoma obtained between 1987 and 2009. To identify genetic lesions that are associated with age at diagnosis in patients with metastatic neuroblastoma. Age groups at diagnosis included infants (0-18 months), children (18 months-12 years), and adolescents and young adults (>12 years). To confirm the findings from this discovery cohort, validation testing using tumors from an additional 64 patients obtained between 1985 and 2009 was also performed. Formalin-fixed paraffin-embedded tumor tissue was used for immunohistochemistry and fluorescent in situ hybridization. Telomere lengths were analyzed using the whole genome sequencing data, quantitative polymerase chain reaction and fluorescent in situ hybridization

  Study EGAS00001000213

• Whole genome and RNA sequencing of paediatric glioblastoma in the ICGC PedBrain project

  Paediatric glioblastoma (pedGBM) is characterised by substantial intertumoural heterogeneity. In order to identify the genetic lesions underlying tumourigenesis, we analysed whole genomes and transcriptomes of pedGBMs and in vitro model systems by next generation sequencing. Novel fusions of the receptor tyrosine kinase MET lead us to investigate targeted therapy using MET inhibitors. This study is part of the International Cancer Genome Consortium PedBrain Tumor Project (ICGC PedBrain, http://www.pedbraintumor.org/).

  Study EGAS00001001139

• Frequent alterations in cytoskeleton remodeling genes in primary and metastatic Chinese lung adenocarcinomas

  The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including themost commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scalesequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.

  Study EGAS00001000982

• Single-cell RNA-sequencing reveals that glioblastoma recapitulates a normal neurodevetlopmental hierarchy

  We discovered a conserved neural tri- lineage cancer hierarchy centered around glial progenitor-like cells. We also found that this progenitor population contains the majority of the cancer’s cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.

  Study EGAS00001004422

• Functional dissection of inherited non-coding variation influencing multiple myeloma risk

  The project aimed at identification of genotype dependent chromatin accessibility in MM patients.

  Study EGAS00001005394

• Multi-omics of Richter syndrome

  Richter syndrome (RS) is the aggressive transformation of Chronic Lymphocytic Leukemia, mostly with Diffuse Large B-Cell Lymphoma histology. While histologically similar, RS and de novo DLBCLs present with different clinical courses. We characterized the RS epigenome by combining genome-wide DNA methylation with transcriptome-sequencing on a large RS cohort.

  Study EGAS00001005495

• Microenvironment subtypes and association with tumor cell mutations and antigen expression in follicular lymphoma

  Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the immune microenvironment of FL. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies.

  Study EGAS00001006052

• High-resolution lung adenocarcinoma expression subtypes identify tumors with dependencies on MET, CDK4, CDK6, and PD-L1

  Lung adenocarcinoma is one of the most common cancer types with various treatment modalities. However, better biomarkers to predict therapeutic response are still needed to improve precision medicine. We utilized a consensus hierarchical clustering approach on 509 LUAD cases from TCGA to identify five robust LUAD expression subtypes. We then integrated genomic (patient and cell line) and proteomic data to help define biomarkers of response to targeted therapies and immunotherapies. This approach defined subtypes with unique proteogenomic and dependency profiles.

  Study EGAS00001006461