7142 results for "canc*"

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• Genome and transcriptome sequence data from a osteosarcoma tumor patient

  Genome and transcriptome sequence data from a osteosarcoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015278

• Genome and transcriptome sequence data from a aggressive fibromatosis tumor patient

  Genome and transcriptome sequence data from a aggressive fibromatosis patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015279

• WGS short read and 10X linked read sequencing of HR Deficient breast cancers

  A set of tumor/normal paired sequencing experiments, performed in short read WGS and 10X linked read whole genomes. BAM files aligned to hg19 are provided. Sample Alias number and Subject ID reflects patient of origin. T/N distinction discriminates between tumor and normal (peripheral blood) tissue.

  Dataset EGAD00001010326

• Global Anaplastic Thyroid Cancer Initiative

  Raw whole genome sequence data(fastq) for the GATCI project

  Dataset EGAD00001003236

• dataset for BGI bladder cancer project

  dataset for BGI bladder cancer project

  Dataset EGAD00001000758

• Whole genome sequencing of breast cancer and related clones

  Paired WGA (whole-genome amplificated) samples from 65 single cell-derived organoids and six fresh single cell-derived organoid samples both of which were established from normal mammary epithelial cells, 84 FFPE LCM (laser-capture microdissection) samples of breast cancer and related clones, 79 fresh-frozen LCM samples of non-cancer lobules of breast cancer patients, and 36 matched germline controls were subjected to whole genome sequencing using NovaSeq 6000 system (Illumina) or DNBSEQ-G400RS (MGI Tech).

  Dataset EGAD00001010833

• RNAseq

  RNAseq of pancreatic cancer organoids.

  Dataset EGAD00001010834

• Melanoma PEACE Dataset

  Dataset for the initial melanoma PEACE paper in Cancer Discovery, March 2023.

  Dataset EGAD00001010877

• Genome and transcriptome sequence data from a multifocal glioblastoma multiforme tumor patient

  Genome and transcriptome sequence data from a multifocal glioblastoma multiforme patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015281

• Genome and transcriptome sequence data from a progressive facial plexiform neurofibroma tumor patient

  Genome and transcriptome sequence data from a progressive facial plexiform neurofibroma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015282

• The dataset for Single molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer

  The dataset for Single molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer includes 57 BAM files from whole genome next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include plasma samples from individuals with and without cancer.

  Dataset EGAD00001010891

• Genome and transcriptome sequence data from a myoepithelioma patient

  Genome and transcriptome sequence data from a myoepithelioma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010938

• Clonal selection after gene therapy in sickle cell disease

  While gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD), the occurrence of myeloid malignancies in clinical trials has prompted concern. To interrogate potential mechanisms underlying increased cancer risk, we used hematopoietic stem cell (HSC) clonal tracking by whole genome sequencing (WGS) to map the somatic mutation and clonal landscape of 2,592 gene modified as well as unmodified single stem and progenitor cells from six SCD patients undergoing gene therapy (7-26 years old, average 12.7× depth). Pre-GT phylogenetic trees in SCD were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified. However, an increased frequency of driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) were seen in both genetically modified and unmodified cells suggested positive selection of mutant clones during gene therapy. This work sheds light on the mutation landscape and HSC clonal dynamics in gene therapy for SCD and highlights enhanced fitness of some HSCs harboring pre-existing driver mutations following gene therapy. Future studies should define the long-term fate of mutant clones including any contribution to expansions associated with myeloid neoplasms.

  Dataset EGAD00001010914

• The dataset for Detecting Liver Cancer Using Cell-Free DNA Fragmentomes

  The dataset for Detecting Liver Cancer Using Cell-Free DNA Fragmentomes includes 444 BAM files from whole genome next-generation sequencing on the Illumina NovaSeq 6000. The samples analyzed include plasma samples from individuals with and without cancer.

  Dataset EGAD00001010931

• Genome and transcriptome sequence data from a pancreatic adenocarcinoma patient

  Genome and transcriptome sequence data from a pancreatic adenocarcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010940

• Genome and transcriptome sequence data from a leiomyosarcoma patient

  Genome and transcriptome sequence data from a leiomyosarcoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010939

• Genome and transcriptome sequence data from a squamous cell carcinoma patient

  Genome and transcriptome sequence data from a squamous cell carcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010941

• Genome and transcriptome sequence data from a non-small cell lung carcinoma patient

  Genome and transcriptome sequence data from a non-small cell lung carcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010942

• Genome and transcriptome sequence data from a breast ductal carcinoma patient

  Genome and transcriptome sequence data from a breast ductal carcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010954

• Genome sequence data from a metastatic rectal carcinoma patient

  Genome sequence data from a metastatic rectal carcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010972

• Genome sequence data from a metastatic paraganglioma patient

  Genome sequence data from a metastatic paraganglioma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010985

• Genome and transcriptome sequence data from a unknown - likely pancreatobiliary / intrahepatic cholangiocarcinoma in liver patient

  Genome and transcriptome sequence data from a unknown - likely pancreatobiliary / intrahepatic cholangiocarcinoma in liver patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001010989

• Genome and transcriptome sequence data from a metastatic ovarian cancer patient

  Genome and transcriptome sequence data from a metastatic ovarian cancer patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001011005

• Genome and transcriptome sequence data from a metastatic breast ductal carcinoma patient

  Genome and transcriptome sequence data from a metastatic breast ductal carcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001011021

• Genome and transcriptome sequence data from a thymoma patient

  Genome and transcriptome sequence data from a thymoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001011039

• Genome and transcriptome sequence data from a rectal adenocarcinoma patient

  Genome and transcriptome sequence data from a rectal adenocarcinoma patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001011040

• 47 urothelial cancer patients WES and 38 RNAseq

  We performed a global mutational landscape analysis using tumor samples from the 47 urothelial cancer patients included in MATCH-R or MOSCATO studies, with advanced metastatic disease and WES available (RNAseq is included for 38 patient samples).

  Dataset EGAD00001011063

• Organoid Derivation Project - GRCh38 - RNAseq (2023-06-22)

  Sequencing of tissue samples and their derived organoids from oesophageal, pancreatic and colorectal cancer patients. . This dataset contains all the data available for this study on 2023-06-22.

  Dataset EGAD00001011092

• Organoid Derivation Project - GRCh38 - WGS (2023-06-22)

  Sequencing of tissue samples and their derived organoids from oesophageal, pancreatic and colorectal cancer patients. . This dataset contains all the data available for this study on 2023-06-22.

  Dataset EGAD00001011093

• Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

  Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

  Dataset EGAD00001011123

• 10x Single Cell Gene Expression Library SCRNA10X_SA_CHIP0163_001

  10x Single Cell Gene Expression library SCRNA10X_SA_CHIP0163_001 for Triple negative breast cancer patient-derived xenograft SA609X7XB03505

  Dataset EGAD00001011219

• RNASeq data from one small cell prostate cancer patient (4 samples from 3 time points)

  RNASeq data from one small cell prostate cancer patient - 4 cancer samples (FFPE) from Patient 1 collected at 3 different time points. mRNA was selected using the Magnetic mRNA Isolation Module (NEB) and sequenced on the Illumina NextSeq 500 as 75bp paired end reads (total read length 150bp).

  Dataset EGAD00001011154

• 10x Single Cell Gene Expression Library SCRNA10X_SA_CHIP0206_002

  10x Single Cell Gene Expression library SCRNA10X_SA_CHIP0206_002 for Triple negative breast cancer patient-derived xenograft SA535X10XB03696

  Dataset EGAD00001011235

• 10x Single Cell Gene Expression Library SCRNA10X_SA_CHIP0014_001

  10x Single Cell Gene Expression library SCRNA10X_SA_CHIP0014_001 for Triple negative breast cancer patient-derived xenograft SA604X6XB01979

  Dataset EGAD00001011251

• 10x Single Cell Gene Expression Library SCRNA10X_SA_CHIP0015_001

  10x Single Cell Gene Expression library SCRNA10X_SA_CHIP0015_001 for Triple negative breast cancer patient-derived xenograft SA604X6XB01979

  Dataset EGAD00001011252

• RNA-seq data from the tumor samples of head and neck cancer patients

  This dataset contains paired-end RNA sequencing data (2x50 bp) from the primary tumors and the recurrences/metastases of 6 head and neck cancer patients.

  Dataset EGAD00001011279

• Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer

  Dataset consists of 216 samples, with each sample having a BAM, BAI and VCF file.

  Dataset EGAD00001011297

• Genome and transcriptome sequence data from a angiosarcoma tumor patient

  Genome and transcriptome sequence data from a angiosarcoma patient, generated as part of the BC Cancer Agency's Pediatric Personalized Onco-Genomics study

  Dataset EGAD00001015290

• Machine Learning Guided Signal Enrichment for Plasma Tumor-burden Monitoring Dataset

  Includes 4 Datasets: 1. 35 Control Plasma WGS samples sequenced on NovaSeq V1.0 Chemistry at the New York Genome Center. Denoted by CTRL-2XX naming scheme. 2. Plasma WGS from 17 patients with Small Cell Lung Cancer. Samples extracted at either Pretreatment or Postoperative at weeks 2 or 3. Denoted by SCLC-XX naming scheme. 3. Plasma WGS from a synthetic mixing study of a high-burden melanoma plasma sample with plasma bag, at estimated tumor concentrations of 10e-3, 10e-4, 10e-5, and 10e-6 for 2 replicates. Denoted by SM-repX naming scheme. 4. Assorted Plasma, Tumor, and Normal WGS from patients with NSCLC expressing high-burden for use in model training. Denoted by NSCLC-2XX naming scheme.

  Dataset EGAD00001011352

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 9 part 1)

  Whole genome sequencing data of 6 high-grade serous carcinoma (HGSC) patients (11 samples) sequenced with MGISEQ-2000

  Dataset EGAD00001011353

• neoALTTO

  RNAseq fastq files for 254 samples for the neoALTTO study of lapatinib, trastuzumab or combination in HER2+ breast cancer patients. Those are pre-treatment baseline samples.

  Dataset EGAD00001011354

• Genome and transcriptome sequence data from a metastatic carcinoma of the lung patient

  Genome and transcriptome sequence data from a metastatic carcinoma of the lung patient, generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001002983

• An MTOR mutation hitchhikes through renal embryogenesis, driving multifocal, multiphenotypic tumours - RNA

  Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the seeding of cells predisposed to disease within mature organs, creating a field effect. We characterise an embryonic cancer mutation that drives multifocal, multiphenotypic renal tumours in a 14-year-old girl. Their shared MTOR mutation, absent from normal tissues, increases protein flexibility which enables a FAT domain hinge to dramatically increase mTORC1 activity. Developmental mutations, not usually detected in traditional genetic screening, have vital clinical importance in guiding prognosis, targeted treatment, and family screening decisions for paediatric tumours.

  Dataset EGAD00001011646

• RNA-sequencing of Human Thyroid cancer cell lines

  RNA-sequencing data of 5 human thyroid cancer cell lines cultured in control conditions

  Dataset EGAD00001011677

• Somatic mutant selection is altered by prior NOTCH1 mutation in ageing esophageal epithelium

  Authors: Charlotte King1, Emilie Abbie1, Joanna C. Fowler1, Irina Abnizova1, Roshan K. Sood1, Swee Hoe Ong1, Michael W. J. Hall1,2, Faye Lynch-Williams3, Benjamin A. Hall4, Philip H. Jones1,2,5 Abstract: In cancer evolution, genome alterations often occur in a specific order, implying selection depends on the prior clonal genotype 1-3. It is unknown if similar constraints operate in normal epithelia. Here, we mapped mutations in normal mid-esophagus of aged UK subjects. Mutant NOTCH1 clones colonized most of the epithelium by age 60 and above 70 tissue was saturated with mutants under strong competitive selection. Mutant TP53 was more strongly selected in donors over 60 years of age. Samples predominantly mutant for NOTCH1 showed increased selection of NOTCH2 mutants and weaker selection of mutant TP53 compared with samples that were mostly NOTCH1 wild type. In mouse esophagus lacking Notch1 we observed strong selection of mutant Notch2 and other genes not selected in wild type esophagus. In normal ageing esophagus, the first driver mutation may change the trajectory of subsequent somatic evolution by altering mutant selection.

  Dataset EGAD00001015258

• The long term effects of chemotherapy on normal blood - Nanoseq dataset

  In developed countries, ~10% of individuals are exposed to systemic chemotherapy for cancer and other diseases. Many chemotherapeutic agents act by increasing DNA damage in cancer cells, hence triggering cell death. However, there is limited understanding of the extent and consequences of collateral DNA damage to normal tissues. To investigate the impact of chemotherapy on mutation burdens and cell population structure of a normal tissue we sequenced blood cell genomes from 23 individuals, aged 3-80 years, treated with a range of chemotherapy regimens. Substantial additional mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but there were differences in burden between different classes of agent, different agents of the same class and different blood cell types. Chemotherapy also induced premature changes in the cell population structure of normal blood, similar to those of normal ageing. The results constitute an initial survey of the long-term biological consequences of cytotoxic agents to which a substantial fraction of the population is exposed during the course of their disease management, raising mechanistic questions and highlighting opportunities for mitigation of adverse effects.

  Dataset EGAD00001015340

• Sequencing data for "Replication timing alterations are associated with mutation acquisition during tumour evolution in breast and lung cancer"

  Repli-seq data for "Replication timing alterations are associated with mutation acquisition during tumour evolution in breast and lung cancer"

  Dataset EGAD00001015363

• To profile the landscape of sebaceous tumours_WES

  Sebaceous tumours are a rare cutaneous cancer with potential for aggressive behaviour. However, limited information is available on these cancers with few published cases. Here we wish to exome sequence these cancers to define the first genomic landscape for this malignancy. We will extract DNA from formalin-fixed, paraffin-embedded (FFPE) cores. Cores may be obtained from lesional and non-lesional tissues of primaries as well as matching metastases. The extracted DNA will be used for exome sequencing. Please note that the dataset was last revised on October 16, 2025.

  Dataset EGAD00001015367

• DNA WGS Short Read Sequence (Illumina NovaSeq) for manuscript titled: "Performance of Somatic Structural Variant Calling in Lung Cancer using Oxford Nanopore Sequencing Technology"

  DNA WGS Short Read Sequence (Illumina NovaSeq) for manuscript titled: "Performance of Somatic Structural Variant Calling in Lung Cancer using Oxford Nanopore Sequencing Technology"

  Dataset EGAD00001015399

• DNA WGS Long Read Sequence (PromethION) for manuscript titled: "Performance of Somatic Structural Variant Calling in Lung Cancer using Oxford Nanopore Sequencing Technology"

  DNA WGS Long Read Sequence (PromethION) for manuscript titled: "Performance of Somatic Structural Variant Calling in Lung Cancer using Oxford Nanopore Sequencing Technology"

  Dataset EGAD00001015400

• Characterising the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER

  Characterising the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER

  Dataset EGAD00001015411

• Somatic mutation in edited cholangiocyte organoids

  Primary human cells cultured in organoid format have great promise as potential regenerative cellular therapies. However, their immunogenicity and mutagenic profile remain unresolved, impeding effective long-term translation to the clinic. In this study we report, for the first time, the generation of human leukocyte antigen (HLA)-I and HLA-II knock-out human expandable primary cholangiocyte organoids (PCOs) using CRISPR-Cas9 as a potential ‘universal’ low-immunogenic therapy for bile duct disorders. HLA-edited PCOs (ePCOs) displayed the same phenotypic and functional characteristics as parental unedited PCOs. Despite minimal off-target edits, duplex sequencing approaches demonstrated that ePCOs and PCOs acquire mutations in culture at similar rates, but without evident selection for cancer-driver mutations. ePCOs induced reduced T cell-mediated immunity and donor-dependent NK cell cytotoxicity in vitro and evaded cytotoxic responses with increased graft survival in humanized mice in vivo. Our findings have important implications for assessment of safety and immunogenicity of primary cell-derived organoid cellular therapies.

  Dataset EGAD00001015456

• Geographic and age-related variations in mutational processes in colorectal cancer - sequence data (Mutographs)

  Geographic and age-related variations in mutational processes in colorectal cancer - sequence data (Mutographs)

  Dataset EGAD00001015485

• The earliest stages of neoplastic transformation in Familial Adenomatous Polyposis

  The succession of somatic genetic events associated with the conversion of a normal colorectal epithelial cell into a colorectal carcinoma constitutes a paradigmatic model of cancer development. Familial Adenomatous Polyposis (FAP) is caused by constitutional inactivating mutations in APC, the central gatekeeper gene of colorectal cancer, and is associated with a substantially increased lifetime-risk of colorectal cancer. To investigate the earliest stages of neoplastic change due to APC inactivation, we microdissected and individually whole genome sequenced 279 histologically normal and abnormal colorectal crypts from 15 individuals with FAP. Histologically normal crypts generally exhibited similar mutation burdens and mutational signatures to normal crypts from wild-type individuals of the same age, with 1/110 carrying a somatic inactivating APC mutation. By contrast, 9/18 aberrant crypt foci carried somatic APC mutations and exhibited modestly increased burdens of some mutational signatures found in normal crypts. 12/13 diminutive adenomatous polyps (less than 5mm diameter) showed somatic APC mutations and carried substantially increased mutation loads of most mutational signatures present in normal crypts. Phylogenetic trees of crypts from aberrant crypt foci and adenomatous polyps revealed that some had acquired their initiating somatic APC mutations decades previously during the first few years of life. The results catalogue the changes in somatic mutation rates, mutational processes and “driver” mutations in cancer genes during the earliest stages of colorectal neoplastic transformation initiated by APC inactivation and highlight the long periods of clonal evolution required for a cancer to develop.

  Dataset EGAD00001015471

• HCA Organoids | Colon - Cancer, WES

  HCA Organoids | Colon - Cancer, Whole Exome Sequencing (WES)

  Dataset EGAD00001015548

• Geographic and age-related variations in mutational processes in colorectal cancer - filtered vcf files (Mutographs)

  Geographic and age-related variations in mutational processes in colorectal cancer - filtered vcf files (Mutographs)

  Dataset EGAD00001015486

• Geographic and age-related variations in mutational processes in colorectal cancer - copy number variants (Mutographs)

  Geographic and age-related variations in mutational processes in colorectal cancer - copy number variants (Mutographs)

  Dataset EGAD00001015487

• HCA Organoids | Colon - Cancer, Multiome Sequencing Data

  Multiome sequencing of patient tissue and patient derived organoids in colon cancer

  Dataset EGAD00001015504

• GBM-Space: Spatial Transcriptomic Profiling of Glioblastoma (10x Genomics - Visium)

  Cancer cells display heterogeneous and dynamic states in glioblastoma, but how these malignant states arise and whether they follow a tractable cellular trajectory across tumours is poorly understood. Here, we generate a deep single cell and spatial multi-region atlas of 12 isocitrate dehydrogenase wild-type (IDH-wt) primary glioblastomas that integrates transcriptomic, epigenomic and genomic analysis to comprehensively characterise their tumour heterogeneity. The datasets in this study include sequencing data from Visium spatial transcriptomic (10x Genomics) profiling of these tumours.

  Dataset EGAD00001015527

• HCA Organoids | Colon - Cancer, Nanopore Sequencing Data

  Nanopore Sequencing Data

  Dataset EGAD00001015536

• Genome and transcriptome sequence data from a malignant peripheral nerve sheath tumor patient

  Genome and transcriptome sequence data from a malignant peripheral nerve sheath tumor patient,generated as part of the BC Cancer Agency's Personalized OncoGenomics (POG) study

  Dataset EGAD00001015583

• RNA-seq dataset of Characterization of UV DNA damage in B-cell precursor acute lymphoblastic leukemia

  Extensive characterization of mutational signature SBS7a in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) samples. We aimed to describe the presentation of SBS7a in BCP-ALL, identify other pediatric cancers presenting with SBS7a, look into the link of SBS7a and UV-light in the context of BCP-ALL and cancers with provable UV exposure, and pinpoint when SBS7a was acquired.

  Dataset EGAD00001015598

• scWGS dataset of Characterization of UV DNA damage in B-cell precursor acute lymphoblastic leukemia

  Extensive characterization of mutational signature SBS7a in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) samples. We aimed to describe the presentation of SBS7a in BCP-ALL, identify other pediatric cancers presenting with SBS7a, look into the link of SBS7a and UV-light in the context of BCP-ALL and cancers with provable UV exposure, and pinpoint when SBS7a was acquired.

  Dataset EGAD00001015601

• Single-Cell Data from "Spatiotemporal T-cell tracking for personalized T-cell receptor T-cell therapy designs in childhood cancer"

  This dataset contains the FASTQ files from the Single-Cell GEx+TCR 10X Genomics data from the study "Spatiotemporal T-cell tracking for personalized T-cell receptor T-cell therapy designs in childhood cancer" (EGAS00001008174)

  Dataset EGAD00001015632

• WXS dataset of Oncogenic and immunological targets for matched therapy of pediatric blood cancer patients: Dutch iTHER study experience

  WXS dataset of Oncogenic and immunological targets for matched therapy of pediatric blood cancer patients: Dutch iTHER study experience

  Dataset EGAD00001015638

• Colorectal Microenvironment Spatial Mapping Dataset

  Two samples derived from a colorectal cancer female patient - tumor tissue and normal adjacent tissue analyzed via Visium Spatial Gene Expression.

  Dataset EGAD00001015675

• Cancer of Low survival and UnMet Need – Pathologist Initiated

  Despite significant advances in diagnostic cancer histopathology, a subset of tumors remain unable to be classified using WHO criteria. The resulting diagnostic uncertainty can result in inappropriate clinical management and negative patient outcomes. We investigated whether combining histopathology with whole genome and transcriptome sequencing (WGTS) could improve the classification of tumors that posed diagnostic dilemmas despite extensive histopathology and standard molecular work-up at a quaternary oncology center. We successfully sequenced 45 tumors from an initial set of 54 unclassified tumors (83% success rate). A confident diagnosis was made for 38/45 tumors (84%). Additionally, potential treatment targets were identified in 21/45 tumors (47%). Theoretical comparison with alternative assays demonstrated that WGTS was uniquely capable of detecting critical diagnostic findings in 15/38 tumors (39%). This work supports augmenting histopathology and standard molecular pathology with WGTS in the classification of difficult-to-diagnose tumors.

  Study EGAS00001008112

• Intratumoural heterogeneity and immune modulation in lung adenocarcinoma of female smokers and never smokers

  Lung cancer is still the leading cause of cancer death worldwide despite declining smoking prevalence in industrialised countries. Although lung cancer is highly associated with smoking status, a significant proportion of lung cancer cases develop in patients who never smoked, with an observable bias towards female never smokers. A better understanding of lung cancer heterogeneity and immune system involvement during tumour evolution and progression in never smokers is therefore highly warranted. We employed single nucleus transcriptomics of surgical lung adenocarcinoma (LADC) and normal lung tissue samples from patients with or without smoking history. Immune cells as well as fibroblasts and endothelial cells respond to tobacco smoke exposure by inducing a highly inflammatory state in normal lung tissue. In the presence of LADC, we identified differentially expressed transcriptional programmes in macrophages and cancer-associated fibroblasts, providing insight into how the niche favours tumour progression. Within tumours, we distinguished eight subpopulations of neoplastic cells in female smokers and never smokers. Through pseudotemporal ordering, we inferred a trajectory towards two differentiated tumour cell states implicated in cancer progression and invasiveness. A proliferating cell population sustaining tumour growth exhibits differential immune modulating signatures in both patient groups. Our results resolve cellular heterogeneity and immune interactions in LADC, with a special emphasis on female never smokers and implications for the design of therapeutic approaches.

  Study EGAS00001006331

• RNA sequencing data of 142 samples from 142 patients with HER2+ breast cancer treated with letrozole or tamoxifen (SOLTI PAMELA trial)

  PAMELA (NCT01973660) is a non-randomized, open-label, multicentric, prospective translational research study in stage I-IIIA HER2+ breast cancer designed to evaluate the ability of the PAM50 intrinsic subtypes to predict pCR in the breast (pCRB) following 18 weeks of neoadjuvant lapatinib and trastuzumab (+/- hormonal therapy if hormone receptor [HR] positive). Patients with HR+ disease received letrozole (if postmenopausal) or tamoxifen (if pre-menopausal). The primary objective was to compare the pCRB rates of the HER2-E versus the non-HER2-E subtypes in the intent-to-treat population.

  Study EGAS00001006410

• Finding structural variation from the human skin fibroblast at the single-cell level

  Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their molecular consequences. We present a computational method, scNOVA, that integrates haplotype-resolved SV discovery with nucleosome occupancy analysis using Strand-seq, to functionally characterize SVs in single cells.

  Study EGAS00001006498

• Whole-genome sequencing in gastric cancer (part2)

  we analysis structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 GCs. Our data demonstrates diverse models of complex SVs operative in GC, which lead to high-level amplification of oncogenes. We find varying proportion of tandem-duplications (TDs) among individuals and identify 24 TD hotspots involving well-established cancer genes such as CCND1, ERBB2 and MYC.

  Study EGAS00001006575

• Real-time analysis of the cancer genome and fragmentome from plasma and urine short and long cell-free DNA using Nanopore sequencing

  Cell-free DNA (cfDNA) can be isolated from blood and/or urine of cancer patients and analyzed with sequencing. Unfortunately, most conventional short-read sequencing methods are technically challenging, labor intensive and time consuming, requiring several days but more typically weeks to obtain interpretable data which are limited by a bias for short cfDNA fragments. Here, we demonstrate that with Oxford Nanopore Technologies sequencing  we can achieve economical and ultra-fast delivery of clinical data from liquid biopsies.   Our ‘ITSFASTR’ approach is able to deliver copy number aberrations, and cfDNA fragmentation profiles in less than 24 hours from sample collection. The tumor-derived cfDNA fraction calculated from lung cancer patient plasma and urine from bladder cancer patients was highly correlated (R=0.98) to the tumor fraction calculated from conventional short-read sequencing of the same samples. cfDNA size profile and fragmentation patterns in plasma and urine exhibited the typical cfDNA features yet with a significantly higher proportion of informative fragments that exceed 300bp, exhibiting similar tumor fraction than shorter size fragments. Notably, comprehensive fragment-end composition and nucleosome profiling near transcription start sites can be determined from the same data.  We propose that ITSFASTR is the first point-of-care solution for obtaining genomic and fragmentomic results from liquid biopsies.

  Study EGAS00001006591

• Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration.

  The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines revealed a unique form of structural variation, termed heterocateny here, characterized by heterogeneous, interrelated, and repetative patterns of concatemerized virus and host DNA segments. Evidence of heterocateny was detected in extrachromosomal and/or intrachromosomal DNA in all cases. Unique breakpoint sequences shared across structurally heterogeneous virus-host concatemers within each cancer facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that unstable virus and virus-host concatemers in ecDNA or integrated form mediate insertion into and excision from chromosomes, capture, rearrangement, and rolling-circle amplification of host DNA, and chromosomal rearrangements. The data indicate that heterocatena is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intra-tumoral heterogeneity and clonal evolution.

  Study EGAS00001006652

• Characterization of MCSP+ melanoma DCC and MelDCC lines

  To dissect the sequence of genotypic and phenotypic progression during early metastatic colonization, we searched for the earliest detectable disseminated cancer cells (DCC) and identified MCSP+ melanoma cells as strong candidates for metastasis founder cells (MFC) in lymph nodes. We isolated MCSP+ DCC from various stages of metastatic colony-formation, performed scRNA-seq and unravelled their phenotypic progression. Further we performed bulk sequencing on patient-derived DCC models (MelDCC) and showed that they exhibit an immunosuppressive activity on CD8 T cells.

  Study EGAS00001006702

• GENOMIC MUTATION LANDSCAPE OF SKIN CANCERS FROM DNA REPAIR-DEFICIENT XERODERMA PIGMENTOSUM PATIENTS

  Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis (TLS) DNA polymerase η (group V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyzed 38 skin cancer genomes from five XP groups. We found that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate. Mutational profile in XP-V tumors revealed the role of polymerase η in the error-free bypass of (i) rare TpG and TpA DNA lesions, (ii) 3’ nucleotides in pyrimidine dimers, and (iii) TpT photodimers. Our study unravels the genetic basis of skin cancer risk in XP and provides insights into the mechanisms reducing UV-induced mutagenesis in the general population.

  Study EGAS00001006732

• Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacterium in the mesenchymal subtype

  The association between colorectal cancer (CRC) clinical variables and Fusobacterium, but not other intra-tumoral bacteria, has been extensively studied. Here we leveraged whole-transcriptome sequencing from 807 CRC tumor samples from the AVANT phase III trial to dually characterize tumor gene expression and intra-tumoral bacteria. After stringent filtering, 74 high-confidence taxa were identified. 17 of these species, including 4 Fusobacterium spp., were classified as orally-derived and had a robust signal within right-sided, MSI-H, and BRAF mutant tumors. Across consensus molecular subtypes (CMS), integration of Fusobacterium animalis presence and tumor gene expression revealed that F. animalis had the greatest number of associations in mesenchymal CMS4 tumors, despite an overall lower prevalence than in immune CMS1 tumors. Pathway analysis within CMS4 revealed that F. animalis, but not other highly prevalent species, was uniquely associated with pathways for collagen degradation and formation as well as IL-6 and IL-1 cytokine signaling. These associations could explain in part why Fusobacterium has been previously associated with reduced survival in mesenchymal populations. Overall, this study identified oral-derived bacteria, including Fusobacterium, as broadly more prevalent in inflamed CRC tumors compared to the other subtypes, and the association of intra-tumoral bacteria on tumor gene expression is context- and species-specific.

  Study EGAS00001006757

• The molecular landscape of homologous recombination deficient, end-stage, high grade serous ovarian cancer

  High grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency, and while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogating mechanisms of resistance, using multiple autopsy samples collected from 15 women with HR-deficient HGSC.

  Study EGAS00001006789

• Non-viral precision T cell receptor replacement for personalized cell therapy

  The T cell receptor (TCR) provides the fine specificity of T cells to recognize mutations in cancer cells 1-3. We developed a clinical-grade approach based on CRISPR/Cas9 non-viral precision genome editing to simultaneously knock-out the two endogenous TCR genes, TCRα (TRAC) and TCRβ (TRBC), and insert in the TRAC locus the two chains of a neoantigen-specific TCR (neoTCR), isolated from the patient’s own circulating T cells using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with refractory solid cancers received up to three distinct neoTCR-transgenic cell products, each expressing a patient-specific neoTCR, in a cell dose-escalation, first-in-human phase 1 clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome, and one grade 3 encephalitis. All had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease, and the other 11 had disease progression as best response on therapy. NeoTCR-transgenic T cells were detected in tumour biopsies post-infusion at frequencies higher than the native TCRs pre-infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs recognizing mutational neoantigens, the simultaneous knock-out of the endogenous TCR and knock-in of the neoTCRs using single-step, non-viral precision genome editing, the manufacturing of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene edited neoTCR T cell products, and the ability of the transgenic T cells to traffic to the patients’ tumours.

  Study EGAS00001006898

• Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

  These data relate to Abbosh et al 2023 'Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA'. Some patients were included in this work that were excluded from the other TRACERx 421 papers (Frankell et al and Al-bakir et al) often due to exclusion criteria in the TRACERx clinical trial. Reasons include partial contamination with C>A artefact mutational signature (CRUK0480 ,0490) which were included for ctDNA detection analyses using high confidence clonal mutations but not clonality analyses, incomplete resection at primary surgery (CRUK0291, 0234, 0230, 0387, 0622) and a concurrent oesophageal second primary cancer (CRUK0498). The primary tissue exome sequencing for these patients that were used in this study are included in this repository. Deep targeted sequencing of (median 200) tumour specific mutations in plasma for 1069 samples from 198 TRACERx patients are also included. Additional details related to these patients and samples can be found in the supplementary or data repositories from Frankell et al and Abbosh et al.

  Study EGAS00001006923

• TNBC ctDNA Targeted Panel

  Circulating tumour DNA (ctDNA) detection in liquid biopsy is an emerging alternative to tissue biopsy, but its utility in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) remains to be well understood. In this study, we determined the presence of early stage TNBC ctDNA detectable actionable mutations with a clinically validated hotspot treatment indication panel. Sequencing of plasma DNA from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in NAT protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

  Study EGAS00001006937

• Bulk_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008282

• Lung Adenocarcinoma Promotion by Air Pollutants

  A complete understanding of how environmental carcinogenic exposures promote cancer formation is lacking. Over 70 years ago, tumour formation was proposed to occur in a two step process: an initiating step which induces mutations in normal tissue, followed by a promoter step which triggers cancer development. Recent evidence has revealed healthy human tissue contains a patchwork of clones harbouring oncogenic mutations.This led us to hypothesise that environmental particulate matter measuring PM2.5, known to be associated with lung cancer risk, might promote lung cancer by acting on pre-existing cells harbouring oncogenic mutations in normal lung tissue. Here we use a combination of WGS and RNA-seq of mouse tumours from pollution-exposed mice to examine the impact of particulate matter on mutagenesis and gene expression respectively.

  Study EGAS00001006951

• PELICAN45 RNAseq Dataset

  To better understand the biology of prostate cancer, we performed RNAseq in cancerous (primary and metastatic) and noncancerous tissues in the PELICAN45 cohort. The PELICAN45 RNAseq samples include androgen-deprived metastasis samples from the PELICAN33 consenting rapid autopsy study participants, whose identifiers are A1, A2, etc. The PELICAN45 RNAseq dataset also includes data from non-androgen deprived metastases in an additional 12 men. These samples are identified as PB50, PB133, etc.

  Study EGAS00001006959

• The impact of mutational clonality in predicting the response to anti-PD-L1/PD-L1 in advanced urothelial cancer

  The advent of immune checkpoint inhibitors (ICI) has radically changed the management and therapeutic treatment landscape for patients with cancer. It has been shown that the use of these inhibitors can result in long-term complete remissions even in cases with advanced stages of the disease. However, only a small fraction of patients respond to the treatment. A better understanding of which factors could drive this clinical benefit is fundamental to building more accurate predictive biomarkers and developing alternative therapeutic options for patients who are unlikely to benefit. In order to address this issue, we have generated and analyzed whole exome sequencing (WES) and RNA sequencing (RNASeq) data from a cohort of metastatic urothelial carcinoma patients (N = 27) treated with ICI such as anti-PD-(L)1 monoclonal antibodies.

  Study EGAS00001007086

• Molecular analysis of cancer genomes in children with Lynch syndrome: exploring causal associations

  Molecular characterization of 20 tumors of 18 children with Lynch syndrome to investigate causality. This characterization includes the investigation of second hits, tumor mutational load, mutational signatures and MMR protein expression.

  Study EGAS00001006992

• Biomarker Screen for Efficacy of Oncolytic Virotherapy in Patient-derived Pancreatic Cancer Cultures

  Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking. We screened fourteen patient-derived PDAC cultures for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H 1PV using live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays. Sensitivity was correlated with transcriptome profiles to identify potential predictive biomarkers for response to OVT. Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the basal-like molecular subtype, the quasi-mesenchymal subtype of PDAC was more sensitive to H-1PV, jin-3, and T-VEC. Expression of viral entry receptors did not correlate with sensitivity to OV treatment. Rather, cellular pathways controlling immunological, metabolic, and proliferative signalling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas cGAS expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures.

  Study EGAS00001007001

• Genome-wide DNA Copy Number Analysis of high hyperdiploid acute lymphoblastic leukemia

  Study EGAS00001007049

• RNA sequencing data of 257 samples from 106 patients with HR+/HER2- breast cancer treated with AC plus paclitaxel or letrozole plus ribociclib (SOLTI-1402 CORALLEEN trial)

  Early-stage Luminal B breast cancer is frequent and is a major cause of breast cancer death due to its poor prognosis. Our proposal aims to study the biology behind the sensitivity and resistance of Luminal B breast cancer to chemotherapy (CHT) or a non-CHT regimen composed of hormone therapy in combination with ribociclib, a CDK4/6 inhibitor. To accomplish this, we first completed the SOLTI-1402 CORALLEEN phase II trial, a study where 106 patients with early-stage Luminal B breast cancer were randomized to standard neoadjuvant CHT for 6 months, or neoadjuvant letrozole and ribociclib for 6 months. After treatment, patients underwent surgery. The primary results of the study, which showed that the response rate to letrozole+ribociclib was similar to CHT, was reported (Prat et al; Lancet Oncol). Tumor biopsies were available at baseline, week 3 and surgery. A total of 257 samples were analyzed using the Illumina TruSeq Stranded Total RNA w/Ribo Zero Gold with MiSeq in TGL (Sequencer NovaSeq S4/PE/100x).

  Study EGAS00001007060

• Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression

  Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects from a 10-year prospective study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as subclonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of genetic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident “pseudoantralized” subtype associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.

  Study EGAS00001007067

• Long-term organoid culture of a small intestinal neuroendocrine tumor

  Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has markedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3 NETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly malignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our understanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit disease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal NET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage. Replicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously without dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents and as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully recapitulate many aspects of the original neuroendocrine tumor.

  Study EGAS00001007093

• Implementation of pediatric precision oncology into clinical practice: The individualized Therapies for Children with cancer program “iTHER”

  iTHER is a prospective national precision oncology program aiming to define tumor molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory pediatric tumors in order to identify relevant aberrations to inform treatment. From April 2017 to April 2021, 302 samples of 253 patients were included. Comprehensive molecular profiling utilizing lcWGS, WES, RNAseq, Affymetrix, and/or 850k methylation profiling was performed for 226 samples. Germline pathogenic variants were identified in 16% of patients. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with priority levels very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%). Diagnosis was revised or refined in 8 patients (3.5%). Spatial and temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analysis. Of 137 patients with follow-up beyond 12 months, 21 molecularly matched treatments were applied in 19 patients (13.9%) with modest response. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates feasibility of comprehensive molecular profiling across all ages, tumor types and stages in pediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants within a clinically relevant timeframe. Therefore, WES and RNAseq is implemented into standard clinical care at the Princess Máxima Center for all children. Improved access to targeted treatments within biology-driven combination trials is required to eventually improve survival.

  Study EGAS00001007099

• Whole Exome Sequencing data of six chRCC tumors corresponding to three patients

  Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients’ primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients’ sensitivity to mTOR inhibition. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.

  Study EGAS00001007104

• RNA sequencing of a glioblastoma PDX cohort

  Patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In this project, we molecularly characterized a comprehensive panel of glioma PDX models with well conserved molecular and pathological features over multiple passages. PDX samples were subjected to next generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in glioblastoma. In summary, we reported a newly established and molecularly characterized panel of glioma PDX models with high relevance for translational preclinical research.

  Study EGAS00001007119

• Molecular analysis of cancer genomes in children with Lynch syndrome: exploring causal associations

  Lynch syndrome (LS) predisposes to cancer in adulthood and is caused by heterozygous germline variants in a mismatch repair (MMR) gene. Recent studies show an increased prevalence of LS among children with cancer, suggesting a causal relationship. For LS-spectrum (LSS) cancers, including high-grade gliomas and colorectal cancer, causality has been supported by typical MMR-related tumor characteristics, but for non-LSS cancers, causality is unclear. This dataset contains 5 patients with Lynch Syndrome from the INFORM registry.

  Study EGAS00001007146

• Spatial and temporal intra-tumoural heterogeneity in advanced High-Grade Serous Ovarian Cancer: implications for surgical and clinical outcomes

  Limited evidence exists on the extent and impact of spatial and temporal heterogeneity of high grade serous ovarian cancer (HGSOC) on tumour evolution and patients surgical and clinical outcome. We investigated this through systematic mapping of multi-site tumours at initial presentation and matched relapse from 49 chemo-naïve HGSOC patients with high tumour load, operated upfront. Our data provides a unique insight into the tumour evolution and metastatic pathways of HGSOC across time and space, how this complexity relates to surgical and clinical outcome and its consequences on clinical decision-making.

  Study EGAS00001007164

• Establishment and characterization of an Epstein-Barr virus-positive cell line from a non-keratinizing differentiated primary nasopharyngeal carcinoma

  Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue. NPC268 can undergo productive lytic reactivation of EBV and is highly tumorigenic in immunodeficient mice. Whole-genome sequencing (WGS) revealed close similarities with the tissue of origin, including large chromosomal rearrangements, while whole-genome bisulfite sequencing (WGBS) and RNA sequencing demonstrated a hypomethylated genome and enrichment in immune-related pathways, respectively.

  Study EGAS00001007172

• Chip_seq_oesophageal_adenocarcinoma_

  There is complex interplay between underlying genetic sequence and epigenetic factors, however this interplay is still illusive. Massively reconstructed cancer genomes can be used in order to better understand this relationship. Six oesophageal adenocarcinoma organoids will be sequenced using long read sequencing technologies and will be profiled for a range of epigenetic marks. Combination of genetic and epigenetic data will allow the thorough characterisation of reference cancer genomes and will provide novel insights into mechanisms of gene regulation. Description: Chip-seq Sequencing of 5 patient derived organoid cell models. Each model was derived from a piece of patient tumour taken following surgical rescetion of the tumour. All model derivations took place with the CGaP facility in Sanger.

  Study EGAS00001007180

• Single_cell_ATAC_sequencing_of_rhabdomyosarcoma_tumour_tissue

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008283

• Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial

  Thirty patients with advanced melanoma were recruited to a clinical trial investigating the therapeutic cancer vaccine, UV1, in combination with pembrolizumab. Whole exome sequencing was performed on melanoma biopsies to determine tumor mutational burden and association with response to therapy. RNA sequencing of matched tumor biopsies to evaluate gene expression profiles at baseline and post-treatment.

  Study EGAS00001007210

• Whole genome sequencing of patients with or at risk for HCC

  Liver cancer is a major cause of cancer mortality worldwide. Screening individuals at high risk, including those with cirrhosis and viral hepatitis, provides an avenue for improved survival, but current screening methods are inadequate. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome analyses to evaluate 724 individuals from the United States, the European Union, or Hong Kong with hepatocellular carcinoma (HCC) or who were at average or high-risk for HCC. Using a machine learning model that incorporated multifeature fragmentome data, the sensitivity for detecting cancer was 88% in an average-risk population at 98% specificity and 85% among high-risk individuals at 80% specificity. We validated these results in an independent population. cfDNA fragmentation changes reflected genomic and chromatin changes in liver cancer, including from transcription factor binding sites. These findings provide a biological basis for changes in cfDNA fragmentation in patients with liver cancer and provide an accessible approach for noninvasive cancer detection.

  Study EGAS00001007249