16624 results for "sec+and+unspecified+malignant+neoplasm"

in 56.03 milliseconds.

• MB_450k_methylation

  450k methylation arrays of primary and relapse tumor of a single case of sonic hedgehog medulloblastoma with Li-Fraumeni syndrome

  Dataset EGAD00010002370

• SNParray copy number dataset

  4 oesophageal cancer derived organoid lines and 2 ovarian cancer derived organoid lines

  Dataset EGAD00010002002

• CNS and systemic relapse in DLBCL

  Microarray data for 230 DLBCL patients

  Dataset EGAD00010001909

• BM-eGFP+ MSC expression arrays

  original population (oMSC) and highly migrative subpopulation (sMSC) of murine eGFP+ bone marrow MSC

  Dataset EGAD00010001265

• EGAD00010000496

  Genome-wide SNP genotyping of African rainforest hunter-gatherers and neighbouring agriculturalists

  Dataset EGAD00010000496

• INSPIRE - Investigator-initiated Phase 2 Study of Pembrolizumab Immunological Response in Metastatic Solid Tumors

  Whole exome and RNA sequencing source data for: Clouthier, D.L., Lien, S.C., Yang, S.Y.C. et al. An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE). j. immunotherapy cancer 7, 72 (2019). https://doi.org/10.1186/s40425-019-0541-0 Bratman S*, Yang SYC*, Iafolla MAJ, Liu Z, Hansen AR, Bedard P, Lheureux S, Spreafico A, Razak AA, Shchegrova S, Louie M, Billings P, Zimmerman B, Sethi H, Aleshi A, Torti D, Marsh K, Eagles J, Cirlan I, Hanna Y, Clouthier D, Lien SC, Ohashi PS, Xu W, Siu LL, Pugh TJ. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nature Cancer. 2020:1:873-881. https://doi.org/10.1038/s43018- 020-0096-5. Yang SYC, Lien SC, Wang BX, Clouthier DL, Hanna Y, Cirlan I, Zhu K, Bruce JP, El Ghamrasni S, Iafallo MAJ, Oliva M, Hansen AR, Spreafico A, Bedard PL, Lheureux S, Razak A, Speers V, Berman HK, Aleshin A, Haibe-Kains B, Brooks DG, McGaha TL, Butler MO, Bratman SV, Ohashi PS, Siu LL, and Pugh TJ. Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity. Nature Comm 2021:12, 5137. https://doi.org/10.1038/s41467-021-25432-7

  Study EGAS00001003280

• Extracellular transcriptome in seminal plasma for non-invasive prostate cancer diagnosis

  A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA (mRNA) profile of seminal plasma has not been interrogated for its biomarker potential in the context of prostate cancer. Here, we investigate the mRNA transcriptome in seminal plasma samples obtained from prostate cancer patients (n=25), patients with benign prostate hyperplasia (n=26) and individuals without prostatic disease (n=6). Seminal plasma harbors a complex mRNA repertoire that reflects prostate as its tissue of origin. The endogenous RNA content is higher in the prostate cancer samples compared to the control samples. Prostate cancer antigen 3 (PCA3), a long non-coding RNA with prostate cancer-specific overexpression, and ATP-binding cassette transporter 1 (ABCA1), known to be involved in the prostate cancer pathogenesis, were more abundant in the prostate cancer group. In addition, twelve high confidence fusion transcripts could be detected in prostate cancer samples, including the bona-fide prostate cancer fusion transcript TMPRSS2-ERG. Our findings provide proof-of-principle that the extracellular transcriptome of seminal plasma can reveal information of an underlying prostate cancer.

  Study EGAS00001005277

• Genomics to select patients with metastatic breast cancer for targeted therapy (microarray_cytoscan)

  Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p<0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.

  Study EGAS00001005584

• Genomics to select patients with metastatic breast cancer for targeted therapy (microarray_oncoscan)

  Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p<0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.

  Study EGAS00001005586

• Genomics to select patients with metastatic breast cancer for targeted therapy (microarray_agilent)

  Cancer progression is driven in part by genomic alterations located in oncogenes or tumor suppressor genes. The genomic characterization of cancers has shown a large interpatient heterogeneity regarding the driver alterations, leading to the concept that generating a genomic profiling by multigene sequencing in patients with cancer could allow selecting effective targeted therapies. While this concept has been broadly implemented in daily practice, there is no evidence that such approach improves patient outcome, and how to optimally select the therapy to administer. A genomic profiling using next generation sequencing and copy number analyses was performed 1462 patients with Her2-non overexpressing metastatic breast cancer included in SAFIR02 Breast trial. 238 of these patients were randomized in two trials between a targeted therapy matched to genomic alteration and a maintenance chemotherapy. The trial shows that targeted therapies matched to genomics improves progression free survival (PFS) when genomic alterations are classified level I/II according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) (adjusted HR: 0.41, 90% CI: 0.27-0.61, p<0.001), but not when alterations are classified beyond level II (unadjusted HR: 1.15, 95% CI: 0.76-1.75). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with mBC.

  Study EGAS00001005587

• Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing

  Dataset EGAD00001000856

• Cancer Genomics, ICR, summary data

  DAC for summary level data from the Cancer Genomics group, Division of Genetics and Epidemiology at the Institute of Cancer Research, Sutton, UK.

  Dac EGAC50000000050

• Picuris Pueblo Genomic Project (Modern Data)

  Data Access Committee for the present-day dataset of the project "Picuris Pueblo oral history and genomics reveal continuity in US Southwest".

  Dac EGAC50000000526

• Neurodevelopment_Nantes_hospital

  The neurodevelopmental team in the genetics unit of Nantes hospital focus on the identification on new genes causing neurodevelopmental disorders through whole-genome and transcriptomics sequencing.

  Dac EGAC50000000542

• Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma

  Dataset EGAD00001010049

• U12 Spliceosome Defect Data Access Committee

  This Data Access Committee controls access to data pertaining to the study of the minor spliceosome and it's role in monogenic diabetes.

  Dac EGAC50000000892

• Sardinia Population SNPs frequencies

  List of SNPs, and their frequencies, extracted from a low pass whole genome sequencing of 3,514 individuals.

  Dataset EGAD00001003141

• KUI6280

  RNA seq data normal and hypomethylation

  Dataset EGAD00001009887

• Somatic cancer gene mutation screening

  Sequencing of colorectal tumors and normal tissue using Ion AmpliSeq Cancer Hotspot Panel V2

  Dataset EGAD00001001010

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

  tissue, organoid and normal bam files for whole exome samples

  Dataset EGAD00001010162

• COVID-19 Postmortem Medulla and Olfactory Mucosa snRNA-seq

  Time-dependent characterization of CNS response in COVID-19

  Dataset EGAD00001009075

• WGBS files for PCGP NBL_MYCN_ATRX

  WGBS files for PCGP NBL_MYCN_ATRX paper titled "MYCN Amplification and ATRX Mutations are Incompatible in Neuroblastoma"

  Dataset EGAD00001004559

• MPB_Bonn

  1000Genomes imputed data set of 581 cases and 417 controls for male-pattern baldness

  Dataset EGAD00001001456

• H3Africa TrypanoGEN+ Fastq

  TrypanoGEN+ data containing fastq files of 183 samples from DRC, Malawi and Uganda using NextSeq500.

  Dataset EGAD00001011666

• The UCSF Low Grade Glioma Genome Project #2"

  Dataset contains WES data from 3 astrocytoma patients: blood as control, primary tumor and recurrent tumor

  Dataset EGAD00001001305

• Chugai colorectal organoid sequencing

  Genomic and transcriptomic characterization of drug-resistant colon cancer stem cell lines.

  Dataset EGAD00001001446

• AML exome sequencing

  Raw data (fastq files) from whole exome sequencing of AML patients (paired diagnosis and complete remission samples)

  Dataset EGAD00001002116

• Bulk RNA-Seq Digital Gene Expression Matrix

  Raw read counts and normalized read counts for each gene

  Dataset EGAD50000002489

• RNAseq of fibroblasts

  RNA sequencing data of fibroblasts from 3 controls and 3 patients with RBMX variants.

  Dataset EGAD50000002371

• HMO-microbiome study dataset, 16S sequencing

  This dataset contains 16S sequencing of fecal and milk samples for HMO-microbiome Lifelines NEXT study

  Dataset EGAD50000000532

• Methylation_PBL_IBD_LTS

  Longitudinal whole-genome DNA methylation profiling of PBL obtained from IBD patients (CD and UC) at two different time points

  Dataset EGAD00010002402

• PDAC organoid genomic heterogeneity

  Two primary tumor-derived PDAC organoids were subjected to SNP array, RNA-seq, and single-cell WGS

  Dataset EGAD00010002408

• cqmuGWAS1

  DNA for 1546 individuals from Chongqing was extract from peripheral blood and genotyped by Illumina Omni Zhonghua-8 version 1 gene chips.

  Dataset EGAD00010001527

• SU2C-MARK Lung Cancer Consortium - Checkpoint Blockade Response Project

  Immune checkpoint inhibitors have become a critical part of the armamentarium against advanced Non-Small Cell Lung Cancer (NSCLC). While early studies have identified Tumor Mutation Burden (TMB) and PD-L1 staining as important biomarkers of response, they remain imperfect predictors. Here we describe a multi-institutional effort as part of the SU2C-MARK Lung Cancer Consortium in which Whole Exome Sequencing (WES) - and in select cases, RNA sequencing – was performed on a large collection of NSCLC samples prior to immune checkpoint blockade therapy, along with matched clinical response data following therapy. (Profiling of a small number of on- or post-treatment samples was also performed.) We anticipate this dataset to be of high value for the development of a deep understanding of the molecular determinants of immune checkpoint blockade response as well as the discovery of novel biomarkers.

  Study phs002822

• Study of Adaptation to Hypoxia in Ethiopian Highlanders via Whole Genome Sequencing

  Although it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome (either exons or a subset of SNPs) or a group of candidate genes, interpretation of the results was limited. We focused our study on Ethiopian highlander populations, which have been found to be well adapted to high altitudes (~3500m). We sequenced and analyze the genomes of 13 high altitude native Ethiopians: 6 individuals of Oromo heritage living on Bale Plateau (labeled "Oromos"), and 7 individuals residing on the Chennek field in the Simien Mountains (labeled "Amhara"). Our study revealed evolutionarily conserved genes that modulate hypoxia tolerance.

  Study phs000647

• Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing

  Adapted from manuscript in review: Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC) but there have been few whole genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. These include highly recurrent tandem duplications involving an upstream enhancer of AR. A subset of cases also displayed a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC nominate new alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the noncoding mCRPC genome remain to be discovered.

  Study phs001577

• The Nurses' Health Study (NHS) GWAS of Mammographic Density

  The Nurses' Health Study is an on-going prospective cohort study of women that was initiated in 1976. This specific study was part of a larger study to advance our knowledge of breast cancer etiology, expand the current knowledge of mammographic density, and clarify the relationship between mammographic density and breast cancer risk. We conducted a nested case control study of breast cancer among women who provided a blood sample. We then targeted our mammogram collection to participants that were selected as part of this nested case-control study (i.e. those who had provided a blood sample). The mammogram closest to the date of blood draw (~1989-1990) was used. We assessed mammographic breast density from digitized film images using a computer assisted thresholding method (Cumulus). The women in this study were genotyped using the Illumina Omni Express Platform.

  Study phs000975

• Methylation Profiles of Cell-Free DNA Using Nanopore Sequencing

  Epigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for detecting and characterizing diseases such as cancer. We developed a strategy using nanopore-based single-molecule sequencing to measure cfDNA methylomes. This approach generated up to hundreds of millions of reads for a single cfDNA sample from cancer patients, an order of magnitude improvement over existing nanopore sequencing methods. We developed a single-molecule classifier to determine whether individual reads originated from a tumor or immune cells. Leveraging methylomes of matched tumors and immune cells, we characterized cfDNA methylomes of cancer patients for longitudinal monitoring during treatment.Control subjects consist of healthy individuals without a positive diagnosis of cancer. cfDNA was obtained through purification of plasma from blood draws. Genomic DNA (gDNA) was derived from extraction of primary tumor tissue or from leukocytes from blood draws.

  Study phs002950

• NHLBI TOPMed: Boston Early-Onset COPD Study

  Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States and the only leading cause of death that is steadily increasing in frequency. This project collected a set of extended pedigrees ascertained through subjects with severe, early-onset COPD. This study has enrolled subjects with severe COPD (forced expiratory volume in one second (FEV1) < 40% predicted) at an early age (< 53 years) without alpha-1 antitrypsin deficiency (a known Mendelian risk factor for COPD). Extended pedigrees are enrolled, primarily in New England, although some more geographically distant subjects have been included. This study has been used for epidemiological studies, familial aggregation analysis, linkage analysis, and candidate gene association analysis. Approximately 80 of the severe, early-onset COPD probands will undergo whole genome sequencing in this project with sequencing data available through dbGaP.

  Study phs000946

• Childhood Cancer Data Initiative (CCDI): Pediatric In Vivo Testing Program - Neuroblastoma

  The goal of NCI's Pediatric In Vivo Testing Consortium (PIVOT) is to advance the development of effective treatments for pediatric cancers through preclinical in vivo testing of novel therapeutic agents. To design impactful experiments that can be rapidly translated to the clinic, PIVOT investigators require comprehensive genomic characterization of the patient-derived xenograft (PDX) models used across the consortium. This robust experimental design enhances collaboration with industry partners by providing proof-of-concept data for drugs in development. As part of this effort, neuroblastoma PDX models are being molecularly characterized to identify promising therapeutic candidates. The molecular profiling includes whole exome sequencing (WES), RNA-seq, MethylEPIC array, CytoSNP array, and DNA fingerprinting for quality control. Additionally, demographic and clinical data (e.g., diagnosis, disease site, disease status) are shared. These characterized PDX models, matched with patient tumors, guide model selection for preclinical drug testing.

  Study phs003163

• RNA sequencing of surgically removed lung adenocarcinoma afterwards treated with immune checkpoint inhibitors

  Patients with lung adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) database were enrolled in the training cohort to establish a prognostic signature based on the expression of tumor-specific amino acid metabolism related genes. The established signature was further investigated against an original cohort, KCC-ICI, of chemotherapy combined with immune checkpoint inhibitors. The signature consisting of nine genes, KYNU, PSPH, PPAT, MIF, GCLC, ACAD8, TYRP1, ALDH2, and HDC, could effectively stratify the OS in LUAD patients. The KCC-ICI cohort confirmed the predictive ability of the established signature in the clinical response to immune checkpoint blockade therapy, which correlated with the infiltration of immune cells (e.g., T lymphocytes and nature killer cells). We discovered that the high signature risk score patients showed a significantly lower concentration of plasma-free ??-aminobutyric acid (AABA).

  Study JGAS000675

• Dysregulation of Alternative Splicing Is a Transcriptomic Feature of Patient Derived Fibroblasts From CAG Repeat Expansion Spinocerebellar Ataxias

  The aim of this study was to characterize transcriptomic changes in patient-derived cell lines of CAG repeat expansion spinocerebellar ataxias (SCAs), using RNA-sequencing (RNA-Seq), to help us better understand disease pathogenesis. The data consists of two SCA1, two SCA3, and one SCA7 cell lines with 5 unaffected controls. Widespread alternative splicing dysregulation was identified across all SCA cell lines. Alternative splicing analysis also revealed that the dysregulation affected disease-relevant pathways with novel skipped-exon splicing events from the RNA-Seq data validated with RT-PCR. These findings are consistent with a previous study that identified robust transcriptomic dysregulation, specifically at the splicing level, in SCA1, -3, and -7 mouse models even at presymptomatic ages. Therefore, alternative splicing has the potential to be used as a biomarker not only in mouse models, but also patient models of repeat expansion SCAs.

  Study phs003759

• The Multiomics Blueprint of the Individual with the Most Extreme Lifespan

  Although centenarians are becoming more common in the demography of human populations, the so-called supercentenarians (over 110 years old) are still a rarity. In Catalonia, the historic nation where the subject lived, the life-expectancy for women is 86 years old, so she exceeded more than 30 years the mean statistical value. In a similar manner that premature aging syndromes, such as Hutchinson-Gilford Progeria and Werner syndrome, can provide relevant clues about the mechanisms of aging; the study of supercentenarians might also shed light in the pathways involved in lifespan. To unfold the biological properties that exhibited such a remarkable human being, we developed a comprehensive multiomics analysis in different tissues of her genomic, transcriptomic, metabolomic, epigenomic and microbiomic landscapes , comparing the results with those observed in non-supercentenarian populations.

  Study EGAS50000000884

• Sequencing data from a highly cost-effective cell-free DNA methylome test

  Plasma cell-free DNA (cfDNA), originating from multiple organs, holds significant potential for non-invasive diagnostics and prognostics. Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci. In contrast, comprehensive profiling of cfDNA methylome can enable simultaneous detection of multiple diseases by capturing organ-specific methylation signatures, thereby offering a holistic view of health, when disease etiology is unclear or when conventional biochemical diagnostics are unavailable. However, deep sequencing required for sensitive detection of methylation abnormalities remains prohibitively expensive, limiting widespread clinical use. To overcome this barrier, we developed MethylScan, a highly cost-effective approach for cfDNA methylome sequencing. We demonstrated its broad clinical utility in a cohort of 1,061 individuals across diverse applications, including multi-cancer detection in general population, liver cancer surveillance in high-risk individuals, liver disease classification, identification of organ abnormalities, and race prediction from cfDNA.

  Study EGAS00001008125

• ALK_inhibitors_in_the_context_of_ALK_dependent_cancer_cell_lines

  Anaplastic lymphoma kinase (ALK) has recently been found to be a critical cancer gene in cases of lung cancer, neuroblastomas and lymphomas. ALK inhibitors have recently shown significant activity in lung cancer patients with tumours that harbour the EML4-ALK gene rearrangement, but already drug-resistance is emerging. We have taken a lung cancer cell line H3122 (with the EML4-ALK rearrangement) and generated clones resistant to a small molecule inhibitor of ALK by serial exposure to the drug over 8 weeks. We now wish to characterise at the exome level whether the acquisiton of resistance has been accompanied by the development of new mutations that we can take forward for further study as the potential mechansims underlying the resistance. We therefore propose to exome sequence the parental NCI-H3122 cell line as well as drug-resistant clones.

  Study EGAS00001000082

• Colorectal advanced adenomas NKI-AvL TGO COCOS series

  Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. About 5% of colorectal adenomas are estimated to progress to CRC. However, it is important to identify which adenomas actually carry a high-risk of progression, because these serve as intermediate endpoints for e.g. screening programs. In clinical practice, adenomas with a size of ≥10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high-risk, although solid evidence for this classification is lacking. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression.For this tissue dataset, we applied low-pass whole genome sequencing to 96 advanced adenomas. Advanced adenomas were classified as lesions with low-risk or high-risk of progression, according to the presence of specific DNA copy number changes (Carvalho et al, CancerPrevRes, 2018).

  Study EGAS00001002952

• CRLF2_sequencing_project_

  I hope to gain insight into novel genetic aberrations present in these patients that will highlightimportant pathways that are involved in this subtype of leukaemia. It would be interesting to see ifthe mutations and pathways that are activated are consistent between the patients, or differencesare observed dependent upon whether the patient has the translocation or the PAR1 deletion. Ofnote is the high association with either numerical gains of chromosome X or numerical/structuralabnormalities of chromosome 21 (Down syndrome, iAMP21) in patients with CRLF2 deregulation. Ihope to find abnormalities linking chromosomes X and 21 to CRLF2 deregulation in BCP‐ALL. Byincluding the three patients that are normal for CRLF2, but have consistent genetic abnormalitiesfound in the experimental cohort, I expect to find genetic differences between these two groupsthat will help us to identify novel molecular targets specific to CRLF2 deregulation.

  Study EGAS00001000080

• Pharmacogenomic landscape of patient-derived cells informs precision oncology therapy

  Outcomes of anticancer therapy vary dramatically among patients, which may be caused by the specific molecular alterations in each patient’s tumor. Precision oncology aims to apply optimal therapies for each tumor based on its molecular characteristics. We have established a resource reporting the genomic and transcriptomic profiles of 462 patient tumor-derived cells (PDCs) across 14 cancer types, together with responses to 60 targeted agents. Compared with long-term cultured cancer cell lines, PDCs better recapitulate the molecular profiles of the original tumors. Among other unreported associations, we identify molecular factors inducing resistance to EGFR inhibitors in glioblastoma, and we suggest repurposing ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, using a retrospective clinical study, we find that PDC-derived sensitivities can be used to predict patient responses.

  Study EGAS00001002515

• Transcriptomic profiles of tumor samples from patients with stage I-III TNBC treated with anthracycline-taxane chemotherapy plus fasting-mimicking diet plus/minus metformin in the context of the BREAKFAST trial (NCT04248998)

  BREAKFAST is a randomized, non-comparative, phase II trial enrolling stage I-III (cT>1cm) TNBC pts treated with neoadjuvant doxorubicin-cyclophosphamide q3w for 4 cycles, followed by weekly paclitaxel for 12 cycles. Pts were randomized 1:1 to receive: CT + triweekly 5-day FMD cycles (arm A), or CT + FMD + daily metformin (1700 mg) (arm B). The primary study objective was to investigate if one or both experimental treatments were able to increase pCR rates when compared to anthracycline-taxane CT alone according to historical data. Secondary/exploratory endpoints included biomarker analyses based on tumor transcriptomics analyses. Specifically, we collected fresh-frozen tumor samples at baseline and 14-21 days after the first treament cycle and we analyzed the RNA-seq profiles to identify early predictors of treatment activity.

  Study EGAS50000000690

• CRLF2_sequencing_project_Exomes

  I hope to gain insight into novel genetic aberrations present in these patients that will highlight important pathways that are involved in this subtype of leukaemia. It would be interesting to see if the mutations and pathways that are activated are consistent between the patients, or differences are observed dependent upon whether the patient has the translocation or the PAR1 deletion. Of note is the high association with either numerical gains of chromosome X or numerical/structural abnormalities of chromosome 21 (Down syndrome, iAMP21) in patients with CRLF2 deregulation. I hope to find abnormalities linking chromosomes X and 21 to CRLF2 deregulation in BCP‐ALL. By including the three patients that are normal for CRLF2, but have consistent genetic abnormalities found in the experimental cohort, I expect to find genetic differences between these two groups that will help us to identify novel molecular targets specific to CRLF2 deregulation.

  Study EGAS00001000081

• Integrative genomic analyses reveal androgen-driven somatic alteration landscape in early-onset prostate cancer

  Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in eleven tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of >10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.

  Study EGAS00001000400

• VIKING Health Study - Shetland

  The Viking Health Study – Shetland, together with ORCADES collectively termed VIKING, aims to identify genes influencing risk factors for common diseases such as heart disease, diabetes, glaucoma and stroke. The genetic research cohort study in Shetland was established to identify genetic variants, both common and rare, increasing risk of disease. This isolated population has a number of characteristics, the most important being the very large number of distant relatives, which are favourable for the identification of rare variants influencing disease risk. This study describes PCR-free paired end whole genome sequencing (TruSeq DNA PCR-Free, Illumina) run on a HiSeqX platform at 30X coverage on 500 individuals from VIKING. Unrelated individuals from the largest families were selected first, followed by those from smaller families, until eventually related individuals were selected to best represent the variation in the full cohort.

  Study EGAS00001003872

• Splicing patterns in SF3B1 mutated uveal melanoma generate shared immunogenic tumor-specific neo-epitopes

  Disruption of splicing patterns due to mutations of genes coding splicing factors in tumors represents a potential source of tumor neo-antigens, which would be both public (shared between patients) and tumor-specific (not expressed in normal tissues). In this study, we show that mutations of the splicing factor SF3B1 in uveal melanoma (UM) generate such immunogenic neo-antigens. Memory CD8+ T cells specific for these neo-antigens are preferentially found in 20% of UM patients bearing SF3B1 mutated tumors. Single cell analyses of neo-epitope specific T cells from the blood identified large clonal T cell expansions, with distinct effector transcription patterns. Some of these expanded TCRs are also present in the corresponding tumors. CD8+ T cell clones specific for the neo-epitopes specifically recognize and kill SF3B1-mutated tumor cells, supporting the use of this new family of neo-antigens as therapeutic targets.

  Study EGAS00001005226

• single nuclei RNASeq of 5 regions of the human prenatal brain

  Data generated through single nuclei RNA sequencing on 5 regions of the brain (frontal cortex, ganglionic eminence, hippocampus, thalamus and cerebellum) from 3 fetuses (two of 14 and one of 15 post-conception weeks, all female). Tissue was acquired from the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) with ethical approval. snRNA-seq libraries were prepared from ∼10,000 nuclei from each sample using Chromium Single Cell 3ʹ (v3) reagents (10X Genomics). Quality control of libraries was performed using the Agilent 5200 Fragment Analyzer before sequencing on an Illumina NovaSeq 6000 to a depth of at least 865 million (median = 1.01 billion) read pairs per library. Raw sequencing data were converted into FASTQ files. For a full description of data generation, please see Cameron et al, Biological Psychiatry 2022, https://doi.org/10.1016/j.biopsych.2022.06.033.

  Study EGAS00001006537

• DNA methylation-based classification of sinonasal tumors [Proteomics data]

  The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. The repository includes the raw mass spectrometry-based proteomics data

  Study EGAS00001006712

• RNA stability controlled by m6A methylation contributes to X-to-autosome dosage compensation in mammals

  In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate for this reduction in dosage compared to two active copies of autosomes, it has been proposed that genes from the active X chromosome exhibit dosage compensation. However, the existence and mechanism of X-to-autosome dosage compensation are still under debate. Here, we show that X-chromosomal transcripts are reduced in m6A modifications and more stable compared to their autosomal counterparts. Acute depletion of m6A selectively stabilises autosomal transcripts, resulting in perturbed dosage compensation in mouse embryonic stem cells. We propose that higher stability of X-chromosomal transcripts is directed by lower levels of m6A, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.

  Study EGAS00001007112

• Analysis of a cohort of familial ademomatous polyposis patients bearing APC gene mutation

  large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC is therefore considered a tumor suppressor gene. While the role of APC in intestinal epithelium homeostasis is well characterized, its importance in immune responses remains ill defined. We investigated an array of immune cell features in FAP subjects carrying APC mutations. A group of 12 FAP subjects and age and sex-matched healthy controls were studied. In particular, the expression of 579 immune response genes was analyzed in whole blood cells using the Nanostring nCounter Human Immunology kit v2. (Cuche C. et al. Frontiers in Immunology, 2023, in press)

  Study EGAS00001007237

• DERMATLAS: Hidradenoma papilliferum_RNAseq

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible.For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.

  Dataset EGAD00001015480

• DERMATLAS: Hidradenoma papilliferum_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible.For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.

  Dataset EGAD00001015481

• Identification of the underlying causal variant in a multi-generational family with autosomal dominant common variable immunodeficiency

  Common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency with an estimated incidence of 1:10,000. It has been apparent for many years that CVID has a genetic component, occurs frequently in families and can have both a recessive or dominant mode of inheritance. In recent years, 4 genes underlying CVID have been identified; however, mutations within in them are estimated to account for no more than 10% of all cases of CVID. We have identified a multi-generational family with autosomal dominant CVID. Genome-wide linkage analysis has mapped the locus underlying CVID in this family to an approximately 9.2 Mb interval on chromosome 3q27.3-q29, between the markers D3S3570 and D3S1265. This locus is distinct from any of the previously mapped susceptibility loci suggesting a novel genetic variant is responsible for disease in this family. The aim of this study is to use exome sequencing of affected (n = 4) and unaffected (n = 4) individuals, in tandem with the available genetic mapping data, to identify the causal variant underlying CVID in this family.

  Dataset EGAD00001000363

• Distinct embryonic phylogenies and driver events of infant Wilms tumor - DNA

  Cancers of adults typically arise through progressive rounds of clonal diversification and intratumoral selective sweeps which generate a long mutational trunk with shorter subclonal branches. Here, we investigated whether tumors of young children exhibit the same phylogenetic configuration. We studied three infants, including two newborns, with the childhood kidney cancer, Wilms tumour, through whole genome sequencing of bulk tissues, of single cell derived organoids, and of microdissections. All three cancers exhibited unusual driver events, with tumours of newborns harbouring FOXR2 rearrangements, delineating a distinct variant of Wilms tumour. Phylogenetic analyses suggest that tumors were seeded in an early, possibly confined window of development. Unusually, following seeding there was extensive polyclonal diversification with little evidence of clonal sweeps, leading to a distinct phylogenetic configuration more reminiscent of normal tissues rather than of adult cancers. These findings indicate that some childhood cancers may diversify via unorthodox phylogenetic pathways.

  Dataset EGAD00001009812

• 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 EGAD00001015259

• 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 EGAD00001015260

• Targeted myeloid panel DNA-Sequencing Mutations Matrix Validation Cohort

  Profiling of co-mutations was done by targeted resequencing using the TruSight Myeloid assay (Illumina, Chesterford, UK) covering 54 genes recurrently mutated in AML: BCOR, BCORL1, CDKN2A, CEBPA, CUX1, DNMT3A, ETV6, EZH2, IKZF1, KDM6A, PHF6, RAD21, RUNX1, STAG2, ZRSR2, ABL1, ASXL1, ATRX, BRAF, CALR, CBL, CBLB, CBLC, CDKN2A, CSF3R, FBXW7, FLT3, GATA1, GATA2, GNAS, HRAS, IDH1, IDH2, JAK2, JAK3, KIT, KRAS, MLL, MPL, MYD88, NOTCH1, NPM1, NRAS, PDGFRA, PTEN, PTPN11, SETBP1, SF3B1, SMC1A, SMC3, SRSF2, TET2, TP53, U2AF1 and WT1. For each reaction, 50 ng of genomic DNA was used. Library preparation was done as recommended by the manufacturer (TruSight Myeloid Sequencing Panel Reference Guide 15054779 v02, Illumina). Samples were sequenced paired-end (150 bp PE) on NextSeq- (Illumina) or (300 bp PE) MiSeq-NGS platforms, with a median coverage of 3076 reads (range 824–30565). Sequence data alignment of demultiplexed FastQ files, variant calling and filtering was done using the Sequence Pilot software package (JSI medical systems GmbH, Ettenheim, Germany) with default settings and a 5% variant allele frequency (VAF) mutation calling cut-off. Human genome build HG19 was used as reference genome for mapping algorithms.

  Dataset EGAD00001008506

• 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 EGAD00001015257

• Somatic mutations in facial skin from countries of contrasting skin cancer risk

  The incidence of non-melanoma skin cancer is 17-fold lower in Singapore compared to the UK1, despite Singapore receiving 2-3 times more year-round ultraviolet radiation (UV)2,3. The ageing epidermis of the skin comprises competing somatic mutant clones4,5, from which such cancers develop. We question if differences in keratinocyte skin cancer incidence are reflected in the mutational landscape by comparing ageing facial epidermis from donors of Singapore and the UK. We find UK skin to be a highly competitive, densely mutated landscape with 4-fold greater mutation burden compared to Singaporean skin and differences in clonal selection by country. We disproportionately observe multiple features common to keratinocyte skin cancers6,7,8 in UK skin, such as UV mutagenesis, copy number aberration and hotspot mutations (in particular TP53 R248W). We conclude that keratinocyte skin cancer incidence is reflected in the somatic clones of non-cancerous epidermis. Finally, we re-analyse squamous cell carcinoma exomes from Korea9 to show, even in low incidence populations, carcinogenesis is driven by UV damage.

  Dataset EGAD00001009666

• Southern African Prostate Cancer Study (SAPCS) Ethnic Disparity

  The cohort (n=130) consists of prostate cancer patients from South Africa (n=123) and Brazil (n=7). For each patient, a pair of blood and tumour samples were collected. The sequencing data was mapped to hg38 reference. Blood BAMs are named with “-B” as suffix and tumour BAMs are named with “-T” as suffix.

  Dataset EGAD00001009067

• Whole genome sequencing in 1038 index cases reveals novel causative genes in pulmonary arterial hypertension

  Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within genes encoding components of the transforming growth factor-ß pathway underlie the majority of heritable forms of PAH. Identifying the missing genetic contribution is challenging, even with genes of large effect size, since it likely involves mutations in genes confined to small numbers of PAH cases. In this study, we performed whole genome sequencing, comparing 1038 PAH index cases to 6385 subjects with other rare diseases. Rare variant analysis identified mutations in novel causal genes, namely ATP13A3, AQP1 and SOX17, and provided independent validation of a critical role for GDF2 in PAH. We detected mutations predicted to be disruptive of function in most, but not all, previously reported PAH genes. Taken together these findings provide new insights into the molecular basis of PAH, and support a central role for endothelial dysregulation in disease pathogenesis.

  Dataset EGAD00001003423

• Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects.

  CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functional consequences of CRISPR-Cas9 gene-editing has not yet been assessed. Utilizing CRISPR-Cas9 knockout screens for 250 cancer cell lines, we demonstrate that targeting structurally rearranged regions, in particular tandem or interspersed amplifications, is highly detrimental to cellular fitness in a gene independent manner. In contrast, amplifications caused by whole chromosomal duplications have little to no impact on fitness. This effect is cell line specific and dependent on the ploidy status. We devise a copy-number ratio metric that substantially improves the detection of gene-independent cell fitness effects in CRISPR-Cas9 screens. Furthermore, we develop a computational tool, called Crispy, to account for these effects on a single sample basis and provide corrected gene fitness effects. Our analysis demonstrates the importance of structural rearrangements in mediating the effect of CRISPR-Cas9-induced DNA damage, with implications for the use of CRISPR-Cas9 gene-editing in cancer cells.

  Dataset EGAD00001004124

• Somatic pathogenic variants in the normal mammary gland of sporadic breast cancer patients

  This dataset contains .fastq files generated by targeted DNA sequencing of 542 cancer-associated and cadidate genes (52 individuals), and targeted duplex sequencing of PIK3CA and TP53 genes (4 individuals).

  Dataset EGAD00001008327

• cfDNA analysis reveals relation of POLR1D amplification to bevacizumab resistance in colorectal cancer patients

  Bevacizumab is an approved anti-angiogenic drug for patients with metastasized colorectal cancer (mCRC) targeting VEGF. The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months and acquired resistance mechanisms are greatly unknown. Using plasma DNA, we studied the evolution of tumor genomes in a cohort of patients with mCRC (n=150) and observed a recurrent focal amplification (8.7% of cases) on chromosome 13q12.2. Analysis of TCGA data (n=619) suggested an association with later stages, which we confirmed by longitudinal plasma analyses. We defined the minimally amplified region and studied the mechanistic consequences of copy number gain of the involved genes. The amplification of one gene, POLR1D, impacted cell proliferation, resulting in upregulation of VEGFA, an important regulator of angiogenesis which has been implicated in the resistance to bevacizumab. In several patients, we observed the emergence of this 13q12.2 amplicon under bevacizumab treatment, which was invariably associated with evolution of therapy resistance. Hence, we describe a novel resistance mechanism against a widely applied treatment in mCRC patients which will impact clinical management .

  Dataset EGAD00001005761

• Targeted capture, whole genome sequencing, and RNAseq to identify rearrangements in B-cell lymphomas

  This study contains whole genome and custom targeted capture sequencing of mature B-cell lymphomas (DLBCL, FL, BL, HGBCL-DH-BCL2, HGBCL-DH-BCL6) to identify translocation breakpoints of common oncogene rearrangements (MYC, BCL2, BCL6). It is complemented by RNAseq data where available. Complete details are available in the publication Hilton et al, 2024, Blood. Capture sequencing: 357 samples; 364 unique libraries; cram file format aligned to hg38 Whole genome sequencing: 12 samples; 12 unique libraries; cram file format aligned to grch37 RNAseq: 257 samples; 257 unique libraries; fastq file format

  Study EGAS50000000328

• Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis

  Single-cell RNA-Sequencing of three primary breast cancers, two primary prostate cancers, and a metastatic melanoma sample from Wu et al. (2021) Genome Medicine study. Each tumour was sequenced across different cryopreservation conditions including Fresh Tissue (FT), cryopreserved single-cell suspensions (CCS), cryopreserved solid tissue fragments (CT) and a cryopreserved after overnight cold storage (CO). Data was generated using the Chromium controller (10X Genomics) and sequenced on the NextSeq platform.

  Dataset EGAD00001007030

• 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 EGAD00001015256

• 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

• ProstOmics - Spatial Transcriptomics

  Spatial transcriptomics data (ST) from 32 human prostate tissue samples originating from 8 prostate cancer patients (5 patients with post-surgery relapse). The ST data was acquired using the Visium Spatial Gene Expression kit which resulted in over 20 000 spatially defined spots for the 32 tissue samples. The raw transcriptomics data is RNA-seq. The individual samples have information on patient origin and sample type (cancer, cancer-adjacent field-effect normal or normal sample far from cancer). Each ST spot has metadata such as sample origin, histology class (stroma, normal epithelium, cancer of various grading etc), number of cells and estimated cell type fractions. Patient metadata include information of age at surgery, time (months) until reported relapse, total follow-up time, pre-surgery PSA, post-surgery T-stage and metastasis status.

  Dataset EGAD50000000603

• EGAD00000000114

  Whole transcriptome sequence data from 18 ovarian clear-cell carcinoma samples and one TOV21G ovarian clear-cell carcinoma cell line

  Dataset EGAD00000000114

• Carcinoma of the oral tongue (OTSCC) genomic landscape characterisation

  18 Exomes for discovery set and 60 Targeted panel for prevalence set

  Dataset EGAD00001001465

• Whole-genome sequencing of a thyroid carcinoma harboring a ETV6-NTRK3 fusion and a NTRK3 G623R mutation (HIPO-021)

  Dataset EGAD00001006243

• Papua New Guinea Pangenome Project Data Access Policy

  This data policy applies to data access to the PNG15 and PNG16 sequencing data as well as derived genomic variant calls.

  Dac EGAC50000000674

• Intellectual disability exome sequencing

  Exome sequencing of ID trios and sibpairs

  Dataset EGAD00001005442

• RNASeq files for GenomePaint paper

  RNASeq files for GenomePaint paper titled "Exploration of coding and non-coding variants in cancer using GenomePaint."

  Dataset EGAD00001006680

• dataset1

  Contains control and PXR KD human small intestinal organoids

  Dataset EGAD00001009785

• Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma

  spatial transcriptomics

  Dataset EGAD00001015262

• RNA-Seq dataset

  10 RNA-Seq bam files including 4 cases with fusion and 6 controls without fusion.

  Dataset EGAD00001004360

• Neuroblastoma sequencing data

  This dataset contains tumor and normal whole exome DNA sequence data for a patient with neuroblastoma

  Dataset EGAD00001008120

• THE MEDICAL RESEARCH COUNCIL – BRAIN BANK (MRC-BB) CONSORTIUM EXOME DATASET

  1461 Neuropathological and clinically characterised cases from the MRC Brain Bank

  Dataset EGAD00001001925

• Patient 16CH

  One file of patient 16 with WGS done on Illumina HiSeq X-Ten. For research purpose and authorised user only.

  Dataset EGAD00001003440

• WGS fastq for EGAS00001004572

  Bulk WGS fastq files for germline and tumours in EGAS00001004572.

  Dataset EGAD00001006902

• WXS files for Zhang PanNBL

  WXS files for Zhang PanNBL paper titled "Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations"

  Dataset EGAD00001005484

• RNAseq

  This dataset contains RNAseq performed on 35 human acute erythroid leukemia patient samples and Xenografts.

  Dataset EGAD00001006076

• Mapping the breast cancer metastatic cascade onto circulating tumour DNA using genetic and epigenetic clonal tracking

  Dataset EGAD00001005507

• MPNST study - scRNA

  10X single nucleus RNA data of one MPNST patient, including one primary and five recurrence regions

  Dataset EGAD50000002565

• MPNST study - WGS data

  WGS data of one MPNST patient, including one primary, five recurrence regions, and blood sample as normal control.

  Dataset EGAD50000002566

• PacBio long-read scRNA-seq

  Full-length single-cell cDNA PacBio Kinnex whole-transcriptome sequencing data for adrenal sampleA and sampleB.

  Dataset EGAD50000002211

• PDiamond Korean Lung Cancer Data

  WES and RNA-seq data of PDiamond Korean lung cancer data

  Dataset EGAD50000000844

• Single-cell transcriptomics of neuroblastoma tumors

  Single-cell, single-nucleus and CITE-sequencing of neuroblastoma tumors with 10X Genomics

  Dataset EGAD50000000328

• scRaCH-seq data targeting BTK and SF3B1

  Data set for scRaCH-seq manuscript. We base call the fast5 using guppy.

  Dataset EGAD50000000235

• RealSeqS ovarian amplicon counts

  Dataset contains text files that describe the chromosome, position, and read count for an amplicon using the RealSeqS assay.

  Dataset EGAD50000000013

• OSC HumanCoreExome Genotypes

  DNA was extracted from saliva samples and genotyping was performed on Illumina Infinium HumanCoreExome beadchips.

  Dataset EGAD00010002375