4116 results for "*oma"

in 65.00 milliseconds.

• Whole genome sequencing of preneoplasia lung adenocarcinoma

  Whole genome sequencing of 42 pulmonary samples including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=5), adenocarcinoma in situ (AIS, N=7), minimally invasive adenocarcinoma (MIA, N=6) and invasive lung adenocarcinoma (ADC, N=8) and adjacent lung tissues (Normal, N=16).

  Study EGAS50000000272

• Whole exome sequencing of preneoplasia lung adenocarcinoma

  Multi-region exome sequencing of 271 pulmonary nodules and matched adjacent lung tissue including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=49), adenocarcinoma in situ (AIS, N=42), minimally invasive adenocarcinoma (MIA, N=37), invasive lung adenocarcinoma (ADC, N=57) and adjacent lung tissues (Normal, N=88).

  Study EGAS50000000270

• Korean WGS

  We sequenced the genomes of 141 Korean never-smoker lung adenocarcinoma patients, excluding EGFR and ALK alterations. We utilized the TruSeq DNA Library Prep Kit and performed by the Illumina NovaSeq 6000 instrument, yielding sequencing paired reads of approximately 150 bp in size. Afterward, we processed the FASTQ files using the GATK Best Practice pipeline.

  Dataset EGAD50000000346

• RNAseq of preneoplasia lung adenocarcinoma

  RNA sequencing of 168 pulmonary samples including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=38), adenocarcinoma in situ (AIS, N=22), minimally invasive adenocarcinoma (MIA, N=19) and invasive lung adenocarcinoma (ADC, N=38) and adjacent lung tissues (Normal, N=62).

  Dataset EGAD50000000395

• Whole genome sequencing of preneoplasia lung adenocarcinoma

  Whole genome sequencing of 42 pulmonary samples including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=5), adenocarcinoma in situ (AIS, N=7), minimally invasive adenocarcinoma (MIA, N=6) and invasive lung adenocarcinoma (ADC, N=8) and adjacent lung tissues (Normal, N=16).

  Dataset EGAD50000000396

• Whole exome sequencing of preneoplasia lung adenocarcinoma

  Multi-region exome sequencing of 271 pulmonary nodules and matched adjacent lung tissue including lung preneoplasia atypical adenomatous hyperplasia (AAH, N=49), adenocarcinoma in situ (AIS, N=42), minimally invasive adenocarcinoma (MIA, N=37), invasive lung adenocarcinoma (ADC, N=86) and adjacent lung tissues (Normal, N=57).

  Dataset EGAD50000000397

• Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions(H021/INF)

  Many rare cancers are not well understood, and pathogenesis-directed therapies are often lacking, resulting in poor patient outcomes. Leveraging two (inter)national precision oncology trials that enroll large numbers of rare cancers, we investigated the clinical, histopathologic, molecular, and functional characteristics of rhabdomyosarcoma (RMS) with fusions of FUS or EWSR1 to the TFCP2 transcription factor, a recently discovered ultra-rare entity whose classification, pathogenesis, and optimal treatment are unclear. Unusually for fusion-driven sarcomas, most cases had highly rearranged genomes, including chromothripsis, and signs of defective homologous recombination DNA repair. All tumors showed extreme expression of a truncated TERT variant and the ALK receptor tyrosine kinase, which was additionally affected by intragenic deletions and aberrant splicing, resulting in the expression of shortened variants in 58% of cases. Three ALK variants were oncogenic in immortalized cells, and patient-derived tumor cells expressing two variants responded to certain ALK inhibitors. Other recurrent alterations included CDKN2A/MTAP co-deletions and mutations in PAPPA2, encoding an IGFBP5-specific proteinase, in 67% and 25% of cases, respectively. DNA methylation analysis, along with 19 other soft-tissue sarcoma classes, revealed a close relationship with undifferentiated sarcoma but not other RMS subtypes, suggesting that TFCP2-rearranged RMS is a separate entity, possibly arising from a distinct cell of origin. Expression of TFCP2 fusions in immortalized human cells blocked late myogenic differentiation and significantly induced genes that were also highly expressed in patient tumors, including ALK, TERT, and two known regulators of skeletal muscle cells, IGFBP5 and PTH1R. Genome-wide chromatin profiling demonstrated direct binding of FUS-TFCP2 to the ALK and TERT loci outside their regular promoters, which correlated with the expression of alternative transcript variants. Finally, FUS-TFCP2 inhibited the repair of DNA double-strand breaks in immortalized cells, rendering them sensitive to treatment with cisplatin. This study provides insight into the pathogenesis and therapeutic vulnerabilities of a new RMS subtype and illustrates the value of linking comprehensive molecular diagnostics and functional annotation within multicenter consortia to improve the understanding and clinical management of rare cancers.

  Study EGAS00001006939

• Single-cell multi-omics of relapse/refractory multiple myeloma patients (Hipo K08K/H067/K43R)

  Therapy resistance in cancers is ingrained in complex clonal dynamics. While the major clonal population in a tumour might respond well to the employed intervention, minor clones will eventually mutate, consequently acquiring a selective advantage and drug resistance. Hence, to improve cancer therapy, it is crucial to understand the mechanisms behind clonal evolution. Here, we applied single-cell transcriptomics and epigenomics, as well as whole-genome sequencing to 15 patients with relapsed/refractory multiple myeloma (RRMM). By profiling longitudinal samples throughout varying treatment regimens, we were able to interrogate patterns of evolution across patients. In particular, by defining clones based on copy number aberrations (CNAs), we found evidence for the majority of clones being diminished but not fully eradicated during treatment.

  Study EGAS00001006538

• Single-cell profiling of co-cultures of GSCCs and macrophages

  Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs – features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets.

  Study EGAS00001007482

• Osteosarcoma_Whole_Genome

  We propose to definitively characterise the somatic genetics of Osteosarcoma cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.

  Study EGAS00001000147

• Single-cell RNA sequencing of 22 Hodgkin lymphoma tumors and 5 reactive lymph nodes

  Hodgkin lymphoma (HL) is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of non-cancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding crosstalk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 HL tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the HL-specific immune microenvironment at single-cell resolution. Library preparation was performed using the 10x Genomics Chromium system, and Illumina sequencing was used to generate 3' gene expression data for every cell. Downstream analysis was performed in R to identify HL-specific microenvironment patterns and identify novel cell populations.

  Study EGAS00001004085

• Radiotherapy_induced_sarcoma

  Whole genome library making will be performed on genomic DNA derived from radiotherapy induced sarcoma samples and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting libraries and mapped to build 37 of the human reference genome to facilitate the identification of mutations

  Study EGAS00001000138

• Genetic landscape of pediatric Osteosarcoma

  We performed whole-genome sequencing of 37 paired tumor/normal OS genomes and analyzed somatically acquired single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes

  Study EGAS00001000263

• Clear cell sarcoma sequencing data

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

  Study EGAS00001006072

• MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Oesophageal_squamous_cell_carcinoma

  The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (Illumina HiSeqX, 40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.

  Study EGAS00001002725

• RNA-seq of Liver Cancer

  The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome (WGS) and whole exome sequencing (WGS), integrated with DNA methylation and RNA sequencing (RNA-seq) data. The present series corresponds to 161 RNA-seq samples from tumors with matched WES or WGS. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.

  Study EGAS00001002879

• Study of non-clear cell renal cell carcinoma

  Study of non-clear cell renal cell carcinoma

  Study EGAS00001000926

• Spatio-temporal evolution of the primary glioblastoma genome

  Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of 38 GBM patients with the initial and recurrent tumor specimens for each individual. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk of TMZ-induced hypermutation for these patients under the standard regimen.

  Study EGAS00001001041

• Identification of gene mutations and fusion genes in patients with Sézary Syndrome

  Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma (CTCL) with an aggressive clinical course. The goal of our study is to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sezary cels, fourteen of them fulfilling the diagnostic criteria of SS. Peripheral blood samples were collected for each patient and CD4+ T-lymphocytes and Granulocytes were isolated. DNA and RNA was extracted for matched normal and tumor materials. Whole exome sequencing was performed on matched normal and tumor tissues of 12 patients and RNA sequencing was performed on 10 patients. For 7 of these patients, we have both exome as well as RNA sequencing data. In this study, we present a complex genomic landscape of Sezary syndrome with several point mutations, copy number variations and fusion events which could contribute to the pathogenesis of SS.

  Study EGAS00001001706

• Spatio-temporal evolution of the primary glioblastoma genome (newly added after 2015)

  Since our genomic analysis of 38 GBM patients, we recruited more cases to further study spatial and temporal evolution of glioblastoma with international collaboration of multiple institutes. The cases in this study includes the whole exome and transcriptome of GBM patients newly recruited in Samsung Medical Center.

  Study EGAS00001001800

• ICGC PedBrain: Deep-sequencing of childhood brain tumors.

  Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.

  Study EGAS00001000215

• Fibroblast heterogeneity and immunosuppressive environment in Human breast cancer

  Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, by combining 6 well-known stromal markers, we identify four CAF subsets (CAF-S1 to CAF-S4) in human breast cancer (BC) that exhibit distinct activation patterns and accumulate differently in BC subtypes.

  Study EGAS00001002508

• Alternative splicing in Shh-MB

  We analyzed alternative splicing with Shh medulloblastoma. This dataset contains bam files of whole genome sequencing from 4 cases. Genomic DNA was isolated from both tumor and matched control specimens. We performed whole genome sequence on Illumina Hiseq.

  Study EGAS00001003220

• Paired exome analysis in urothelial carcinoma

  In this study we characterized genomic alterations in two to five metachronous tumors from 29 patients initially diagnosed with early stage disease. Fourteen patients (32 tumors) had non progressive disease (NPD) and 15 patients (34 tumors) had progressive disease (PD). Whole exome sequencing (WES, ~50x mean read depth), Ultra deep targeted sequencing (~6,809x mean read depth) and whole transcriptome RNA-seq was performed for all samples. In addition multiregional WES was performed on 8 adjacent regions from a single tumor.

  Study EGAS00001001686

• glioblastoma and glioblastoma stem cells (GSCs), RNA-seq and WGS

  Characterization of glioblastoma tumors and glioblastoma stem cells (GSCs) lines via RNA-seq and/or WGS profiling.

  Study EGAS00001004395

• Revealing active mutational processes in tumours using DigiPico/MutLX at unprecedented accuracy

  Active mutational processes in a tumor result in genetic micro-heterogeneity that can determine the tumor’s evolutionary trajectory. Identification of these processes by studying micro-heterogeneity can unveil novel aspects of tumor evolution with potential therapeutic implications. Such studies, however, are inherently problematic because of the discovery of excessive false positive mutations. Here we report the optimization and validation of a robust whole genome sequencing and analysis pipeline (DigiPico/MutLX) that virtually eliminates false positive results. Using our method, we identified, for the first time, a sub-clonal local hyper-mutation (kataegis) event in a recurrent ovarian carcinoma, which was unidentifiable from the bulk WGS data of the same tumor. Overall, we propose DigiPico/MutLX method as a powerful framework for the reliable study of genetic micro-heterogeneity in tumor and normal tissues.

  Study EGAS00001003555

• Whole genome sequencing with linked reads of pediatric glioblastoma samples

  Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand mechanisms of tumor evolution in this cancer, we performed whole genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Clonal composition rapidly evolved at recurrence, with less than 8% of non-synonymous single nucleotide variants being shared in diagnostic-recurrent pairs. In order to track the origins of the mutational events we observed in pGBM, we generated whole genome datasets for two patients and their parents. These trios showed that genetic variants could be (i) somatic, (ii) inherited from a healthy parent, or (iii) arose de novo in the germlines of pGBM patients. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating progenitor-like cells and to non-dividing cells. Interestingly, radiation and anti-mitotic chemotherapeutics did not increase overall tumor burden upon recurrence. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, since slow-cycling cell populations are expected to be less prone to genotoxic stress induced by these treatments and to accumulate few mutations. Our results highlight the need for new targeted treatments that account for the complex functional hierarchies and genomic heterogeneity of pGBM.

  Study EGAS00001003432

• A Single-Cell Atlas of the Multicellular Ecosystem of Primary and Metastatic Hepatocellular Carcinoma

  Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generated a single-cell atlas of the multicellular ecosystem of HCCs from four relevant sites. Antitumor central memory T (TCM) cells were found in tertiary lymphoid structures (TLSs). Chronic HBV/HCV infection increases infiltration of CD8+ T cells in tumors but aggravates T cell exhaustion. We identified CD11b+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and two distinct differentiation trajectories contribute to their accumulation. We further demonstrated CD11b+ TAMs promote HCC cells invasion and migration, and angiogenesis. We characterized the heterogeneous subpopulations of malignant hepatocytes and their multifaceted roles in shaping the immune microenvironment. Finally, we identified seven TME subtypes that can predict patient prognosis. Collectively, this large-scale atlas deepens our understanding of the ecosystem in primary and metastatic HCCs, might facilitating the development of new immune therapy strategies for this malignancy.

  Study EGAS00001004468

• Genetic landscape of pediatric Rhabdomyosarcoma

  We performed whole-genome sequencing of 13 paired tumor/normal Rhabdomyosarcoma genomes and analyzed somatically acquired single nucleotide variations SNVs, insertion/deletions, structural variations and copy number variations in the cancer genomes

  Study EGAS00001000256

• Identification and functional characterisation of a rare MTTP variant underlying familial non-alcoholic fatty liver disease

  We identified a rare causal variant in MTTP, c.1691T>C p.I564T (rs745447480) encoding microsomal triglyceride transfer protein (MTP) causing progressive non-alcoholic fatty liver disease with cirrhosis and hepatocellular carcinoma unrelated to metabolic syndrome, without manifestations of abetalipoproteinemia, in a four generation family with South Asian ancestry. Variant-expressing hepatocyte-like-cells (HLCs) derived from human induced pluripotent stem cells generated from homozygous donor skin fibroblasts had lower lipoprotein ApoB secretion, compared to wild type cells. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, production of reactive oxygen species, delineating the progression of disease associated with homozygosity for MTTP p.I564T

  Study EGAS00001005254

• Evolutionary predictability of genetic versus non genetic resistance to anticancer drugs in melanoma

  Therapy resistance arises from heterogeneous drug-tolerant persister cells or minimal residual disease (MRD) through genetic and nongenetic mechanisms. A key question is whether specific molecular features of the MRD ecosystem determine which of these two distinct trajectories will eventually prevail. We show that, in melanoma exposed to MAPK therapeutics, emergence of a transient neural crest stem cell (NCSC) population in MRD concurs with the development of nongenetic resistance. This increase relies on a GDNF-dependent signaling cascade, which activates the AKT survival pathway in a focal adhesion kinase (FAK)-dependent manner. Ablation of the NCSC population through FAK inhibition delays relapse in patient-derived tumor xenografts. Strikingly, all tumors that ultimately escape this treatment exhibit resistance-conferring genetic alterations and increased sensitivity to ERK inhibition. These findings identify an approach that abrogates the nongenetic resistance trajectory in melanoma and demonstrate that the cellular composition of MRD deterministically imposes distinct drug resistance evolutionary paths.

  Study EGAS00001005314

• A renal cell carcinoma tumorgraft platform to advance precision medicine

  Study EGAS00001005516

• UQCCR/QCMG brain metastasis sequence analysis

  The present study, conducted by the UQCCR and QCMG at the University of Queensland, investigated the genomic landscape of brain metastases from 36 patients (with matched normal samples) that originated from a range of primary tumour sites (including breast (11), lung (18), melanoma (6) and oesophageal (1)) utilizing Illumina 2500 HiSeq Exome sequencing. Somatic substitutions were identified using a dual qSNP/GATK calling strategy. The Pindel tool was used to determined short insertions and deletions. Key biological pathways were investigated using pathway analysis tools. It is envisaged that the current work may provide important biological insights into the genomic characterization and evolution of brain metastasis and additionally identify druggable targets of clinical relevance.

  Study EGAS00001000722

• Genome-wide cell-free DNA termini in patients with cancer

  The structure, fragmentation pattern, length and terminal sequence of cell-free DNA (cfDNA) is under the influence of nucleases present in the blood. We hypothesized that differences in the diversity of bases at the end of cfDNA fragments can be leveraged on a genome-wide scale to enhance the sensitivity for detecting the presence of tumor signals in plasma. We surveyed the cfDNA termini in 72 plasma samples from 319 patients with 18 different cancer types using low-coverage whole genome sequencing. The fragment-end sequence and diversity were altered in all cancer types in comparison to 76 healthy controls. We converted the fragment end sequences into a quantitative metric and observed that this correlates with circulating tumor DNA tumor fraction (R = 0.58, p < 0.001, Spearman). Using these metrics, we were able to classify cancer samples from control at a low tumor content (AUROC of 91% at 1% tumor fraction) and shallow sequencing coverage (mean AUROC = 0.99 at >1M fragments). Combining fragment-end sequences and diversity using machine learning, we classified cancer from healthy controls (mean AUROC = 0.99, SD = 0.01). Using unsupervised clustering we showed that early-stage lung cancer can be classified from control or later stages based on fragment-end sequences. We observed that fragment-end sequences can be used for prognostication (hazard ratio: 0.49) and residual disease detection inresectable esophageal adenocarcinoma patients, moving fragmentomics toward a greater clinical implementation.

  Study EGAS00001005738

• scRNA-seq of LN and lymphoma stroma

  The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, in lymphomas, reportedly underlie lymphomagenesis. However, understanding of lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even in normal human lymph nodes (LNs). Here, we constructed a single-cell transcriptome atlas of >100,000 NHCs collected from 27 human samples, including LNs and various nodal lymphomas, revealing 30 distinct subclusters, including some that were previously unrecognized. Notably, this atlas was highly useful for comparative analysis with lymphoma NHCs, which revealed an unanticipated landscape of subcluster-specific changes in gene expression and interaction with malignant cells in follicular lymphoma NHCs, facilitating our understanding of stromal remodelling in lymphoma and potentially suggesting novel biomarkers. Our study largely updates NHC taxonomy in human LNs and pertains to analysis of disease status, providing a rich resource and deeper insights into LN and lymphoma biology and offering to advance lymphoma management and therapy.

  Study EGAS00001005732

• Genome-wide cell-free DNA termini in patients with cancer

  The structure, fragmentation pattern, length and terminal sequence of cell-free DNA (cfDNA) is under the influence of nucleases present in the blood. We hypothesized that differences in the diversity of bases at the end of cfDNA fragments can be leveraged on a genome-wide scale to enhance the sensitivity for detecting the presence of tumor signals in plasma. We surveyed the cfDNA termini in 72 plasma samples from 319 patients with 18 different cancer types using low-coverage whole genome sequencing. The fragment-end sequence and diversity were altered in all cancer types in comparison to 76 healthy controls. We converted the fragment end sequences into a quantitative metric and observed that this correlates with circulating tumor DNA tumor fraction (R = 0.58, p < 0.001, Spearman). Using these metrics, we were able to classify cancer samples from control at a low tumor content (AUROC of 91% at 1% tumor fraction) and shallow sequencing coverage (mean AUROC = 0.99 at >1M fragments). Combining fragment-end sequences and diversity using machine learning, we classified cancer from healthy controls (mean AUROC = 0.99, SD = 0.01). Using unsupervised clustering we showed that early-stage lung cancer can be classified from control or later stages based on fragment-end sequences. We observed that fragment-end sequences can be used for prognostication (hazard ratio: 0.49) and residual disease detection inresectable esophageal adenocarcinoma patients, moving fragmentomics toward a greater clinical implementation.

  Study EGAS00001005747

• Genome-wide cell-free DNA termini in patients with cancer

  The structure, fragmentation patterns and terminal sequences of cell-free DNA (cfDNA) are altered by nucleases and biological mechanisms in the blood of cancer patients. The cfDNA fragment-end composition recovered from low coverage WGS (<1 fold coverage) using a bespoke software (FrEIA) is aberrant in the plasma from cancer patient (n = 418, 655 samples) compared to controls (n = 117). As a standalone test FrEIA allows detection down to ~0.2% tumor fraction in vitro and in silico at 95% specificity, leading to a sensitivity of ~71% for detecting lung cancer (14/22 stage I-II, 27/38 stage III, 92/127 stage IV) and ~68% for detecting esophageal adenocarcinoma (26/44 stage II, 46/62 stage III). Additional cfDNA biological patterns can be combined with FrEIA increasing the diagnostic potential of low coverage WGS at minimal cost (mean AUROC = 0.96). Integrating multiple cfDNA biological signal augments the diagnostic performance of liquid biopsy.

  Study EGAS00001006142

• Gene expression profiling of HGCC patient-derived Glioblastoma Cell Lines (ISPA-GBM)

  Study EGAS00001006814

• Profiling of childhood neuroblastoma and the immune microenvironment by single-cell sequencing of RNA and TCR

  Neuroblastoma tumor cells and their tumor microenvironment are studied by single-cell RNA sequencing of primary neuroblastoma tumors and neuroblastoma-infiltrated tissues/metastases. Both diagnostic samples, taken pre-treatment and samples taken after induction chemotherapy at surgical resection and biopsies from relapse samples are included.  For a number of patients single-cell RNA sequencing of blood samples (controls) are included and additionally we performed single-cell T cell receptor sequencing (TCR) on the tumor and blood samples. With this study, we will focus on identifying differences in tumor cells and their (immune) microenvironment 1) before and after treatment or at relapse and 2) between primary tumors and infiltrated tissues/metastases. Moreover, with TCR sequencing we aim to unveil immune cell dynamics in patients with neuroblastoma.

  Study EGAS00001006823

• Bolleboom-Gao peri-tumoral snRNA-seq glioblastoma dataset 2022/A

  Bolleboom-Gao peri-tumoral snRNA-seq glioblastoma dataset 2022/A

  Study EGAS00001006935

• Genome-wide cell-free DNA biological patterns in patients with cancer

  The structure of cell-free DNA (cfDNA) is altered in the blood of cancer patients. From whole genome sequencing we retrieved the cfDNA fragment-end composition using a new software (FrEIA), as well as the cfDNA size and tumor fraction in three independent cohorts (n=925 cancer from >10 types and 321 control samples). At 95% specificity, we detect 72% of cancer samples using at least one cfDNA measure, including 64% of early-stage cancer (n=220). cfDNA detection correlates with a shorter overall (p=0.018) and recurrence-free (p=0.006) survival in patients with resectable esophageal adenocarcinoma. Integrating cfDNA measures with machine learning in an independent test set (n=396 cancer, 90 controls) achieve a detection accuracy of 82% and AUROC of 96%. In conclusion, harnessing the biological features of cfDNA can improve at no-extra cost the diagnostic performance of liquid biopsies.

  Study EGAS00001007400

• The Genetic Landscape of Ocular Adnexa MALT Lymphoma Reveals Frequent Aberrations in NFAT and MEF2B Signaling Pathways

  A comprehensive constellation of somatic non-silent mutations and copy number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NFkB, NOTCH and NFAT signaling pathways. One of the most commonly altered genes is CABIN1, a calcineurin inhibitor acting as a negative regulator of the NFAT and MEF2B transcriptional activity. CABIN1 deletions enhance BCR-stimulated NFAT and MEF2B transcriptional activity, while CABIN1 mutations enhance only MEF2B transcriptional activity by impairing binding of mSin3a to CABIN1. Our data provide an unbiased identification of genetically altered genes that may play a role in the molecular pathogenesis of OAMZL and serve as therapeutic targets.

  Study EGAS00001006631

• Genomic evolution and transcriptional changes in the evolution of prostate cancer into neuroendocrine and ductal carcinoma types (RNAseq)

  Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.

  Study EGAS00001007428

• Genomic evolution and transcriptional changes in the evolution of prostate cancer into neuroendocrine and ductal carcinoma types

  Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.

  Study EGAS00001007412

• 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

• Spatial tumor microenvironment characterization and outcome of relapsed/refractory classic Hodgkin lymphoma

  About half of relapsed or refractory classic Hodgkin lymphoma (r/r CHL) patients succumb to their disease after high dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT). Here, we aimed at describing spatially resolved tumor microenvironment (TME) ecosystems to establish novel biomarkers associated with treatment failure in r/r CHL.

  Study EGAS00001007261

• ICGC Oesophageal adenocarcinoma - Barrett's samples

  The oesophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s oesophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.

  Study EGAS00001000726

• Enhancing OSCC Prediction: The Prognostic Power of WPOI and Tumor Budding, and the Limited Impact of Molecular Resection Margins

  This dataset contains sequences with results of mutations observed in patients with oral squamous cell carcinoma. Mutations were detected by NGS in tumor tissue, tumor margins, and peripheral blood as a healthy control. Study was using a panel of 88 cancer-related genes, which were selected based on a literature search.

  Study EGAS50000000074

• Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient

  Single cell RNA and TCR sequencing of gamma delta T cells from two Merkel cell carcinoma patients

  Study EGAS50000000102

• RNA-Seq data from tumor samples collected from 12 UTSW translocation renal cell carcinoma (tRCC) patients.

  This study investigates differentially expressed genes associated with the progression of translocation renal cell carcinoma (tRCC) by analyzing RNA-Seq data from 23 tumor samples obtained from 12 patients. The samples were collected from affiliated hospitals of the University of Texas Southwestern Medical Center (UTSW), including Parkland Hospital and Children’s Medical Center. RNA isolated from tumor samples was sequenced using the Illumina platform.

  Study EGAS50000000127