12214 results for "cancer rna-seq"

in 60.70 milliseconds.

• scKaryoSeq of CRISPR-Cas9 edited primary human T cells

  To explore T cell-intrinsic driving forces of CRISPR-induced aneuploidy at the TRAC gene locus, we performed scKaryo-seq (Bolhaqueiro et al., Nature Genetics 2019). We compared the impact of the small molecule pifithrin-alpha in activated TRAC KO T cells. In a separate experiment, we determined the effect of pifithrin-alpha on non-activated T cells edited at the TRAC locus or treated with non-targeting Cas9 RNPs.

  Dataset EGAD50000000929

• CITE-seq AdaptNK

  CITEseq was performed as outlined in Biolegend ‘TotalSeqTM-A Antibodies and Cell Hashing with 10x Single Cell 3' Reagent Kit v3 3.1 Protocol’ with minor modifications, using Biolegend oligo-conjugated antibodies and streptavidin TotalSeq reagents. Briefly, ADAPT-NK cells were stained with CD56-biotin mAb (Miltenyi, clone REA196), followed by TotalSeq antibodies and streptavidin-PE and Live/Dead Aqua (Invitrogen). Cells were subsequently sorted for viable CD56+ cells by flow cytometry.

  Dataset EGAD50000000329

• WGS of cell line MMML-seq / MALY-DE tumor_4167452

  This dataset contains the aligned whole genome sequencing data of cell line 380. This cell was established from the peripheral blood of a 15-year-old boy with acute lymphoblastic leukemia at relapse, showing an immature phenotype and carrying an IGH-MYC (t(8;14)) as well as an IGH-BCL2 (t(14;18)) chromosomal translocation. The sequencing was performed on an Illumina X-ten sequencer.

  Dataset EGAD00001004090

• Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls

  We created three technical replicates of cell-free DNA from AML patient plasma to assess batch effects and utility of spike-in controls for the cfMeDIP-seq method. Each set of samples were given to three different technicians with slightly different protocols. Details can be found in Wilson et al. "Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls".

  Dataset EGAD00001006986

• RNAseq and ATACseq data

  RNAseq and ATACseq data for the FMF patients and healthy control. The RNAseq data was sequenced on a BGI MGI G400 machine, with PE100 reads. ATAC-seq libraries were prepared with Illumina Nextera primers and sequenced on NovaSeq 6000 platform with 50bp paired-end sequencing, where each sample was sequenced to approximate 60 million reads.

  Dataset EGAD00001010304

• Strand-seq data of primary acute myeloid leukemia patient samples with complex karyotype

  In this study, we aimed to identify somatic structural variation of acute myeloid leukemia with complex karyotype (CK-AML) at the single-cell level and to investigate its direct consequence on the nucleosome occupancy using scNOVA approach. For this purpose, we performed strand-specific single-cell sequencing of primary leukemia samples from four CK-AML patients. We also performed strand-specific single-cell sequencing of two patient-derived xenografts (PDXs).

  Dataset EGAD00001011172

• Center for Sub-Cellular Genomics

  A cell is a highly complex system with distributed molecular physiologies in structured sub-cellular compartments whose interplay with the nuclear genome determine the functional characteristics of the cell. A classic example of distributed genomic processes is found in neurons. Learning and memory require modulation of individual synapses through RNA localization, localized translation, and localized metabolites, such as those from dendritic mitochondria. Dendrites of neurons integrate distributed synaptic signals into both electrical and nuclear transcriptional response. Dysfunction of these distributed genomic functions in neurons can result in a broad spectrum of neuropsychiatric diseases such as bipolar and depressive disorders, autism, among others. The Center for Sub-Cellular Genomics' (CSG) mission is to develop new technologies to enable the dissection of complex genomic interactions within a single cell. New technologies include methods to target DNA and RNA sampling at sub-cellular resolution in live cells; high-throughput isolation and microfluidics chemistry for sub-cellular fractions; sub-cellular resolution mass-spectrometry; and computational tools for analysis of sub-cellular genomics data. The new technologies developed by CSG will enable the broader genomics community to associate sub-cellular processes to cell function and dysfunction. These technologies will be utilized in the center to generate a comprehensive atlas of genomic signatures of sub-cellular compartments in the mammalian neuron system. The technologies and neuron-focused data obtained here will be relevant to neurodegenerative and neuropsychiatric diseases including schizophrenia, depression, autism spectrum disorder, traumatic brain injury, and Alzheimer's.

  Study phs002120

• Platelet RNAseq data for SLFN14 K219N patients

  Pathogenic missense variants in SLFN14, which encodes an RNA endoribonuclease protein that regulates rRNA degradation, are known to cause inherited thrombocytopenia with impaired platelet aggregation and ATP secretion. Despite rather mild laboratory defects, these patients display an obvious bleeding phenotype. The function of SLFN14 in megakaryocyte (MK) and platelet biology is unknown. This study aims to characterize the platelet transcriptome in patients with a SLFN14 K219N variant and model the disease in the immortalized megakaryocyte cell line imMKCL. Total platelet RNA was sequenced for two patients and 19 healthy controls. Differential gene expression analysis yielded a total of 2999 and 2888 significantly (|log2FC|>1, FDR<0.05) up- and downregulated genes, respectively. Remarkably, these downregulated genes were not enriched for any biological pathway while upregulated genes were enriched for pathways involved in (mitochondrial) translation and transcription with a significant upregulation of 134 ribosomal protein genes (RPG). Heterozygous and homozygous SLFN14 K219N imMKCL showed a defect in MK differentiation that aggravated during cell passaging of undifferentiated cells and in proplatelet formation. SLFN14 defective platelets and MK showed signs of rRNA degradation while this was absent in undifferentiated imMKCL cells. Upregulation of RPG through increased mTOR signaling in SLFN14 K219N MK seems to be a compensatory response for rRNA degradation. Indeed, mTOR inhibition with rapamycin resulted in further enhanced rRNA degradation in SLFN14 K219N MK. Taken together, our study indicates dysregulation of mTOR-regulated ribosomal biogenesis as the disease mechanism for SLFN14-related thrombocytopenia.

  Study EGAS00001006339

• The Genomic Complexity of Primary Human Prostate Cancer

  Seven primary prostate cancers and their paired normal counterparts were DNA-sequenced on a massively parallel sequencing platform. This approach was taken to investigate the genomes for mutations and genomic alterations that would be undetectable by lower-resolution methods. As result, tumors containing chains of balanced rearrangements that occurred within or adjacent to known cancer genes were discovered.

  Study phs000330

• Complex Landscapes of Somatic Rearrangements in Human Breast Cancer Genomes

  We have used massively parallel paired end sequencing strategies to reconstruct the genomic landscape of 24 breast cancer genomes, through the identification and characterization of 2166 somatically acquired genomic rearrangements. These studies have revealed considerable complexity in the patterns of structural variation, identified novel fusion genes and unveiled new insights into the complex structure of amplicons.

  Study EGAS00000000062

• ER___HER2___PR__breast_Cancer_genome_sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from X triple negative breast cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting X exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000197

• Variant analysis on FFPE specimen from NSCLC patients (OCAPlus)

  This study assessed the presence of somatic variants via the Oncomine Comprehensive Panel Plus panel (ThermoFisher) for commonly mutated cancer genes and measure tumor mutational burden using next-generation sequencing. It was performed on genomic DNA from FFPE tissue of tumor resections. Mutations were used to draw OncoPrints and to assess TMB in relation with response metrics.

  Study EGAS50000001136

• 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

• TMD_AMLK_Exome_Study

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 20 Primary Acute Megakaryocytic Leukemia samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes

  Study EGAS00001000027

• Breast_Cancer_Exome_Sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 100 breast cancers of all subtypes and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 200 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000211

• Age-related remodeling of apparently normal esophageal epithelia by common cancer drivers

  Driver mutated clones multi-focally emerged from early adulthood and over years, increase their number and size, ultimately remodeling the entire esophageal epithelia in extreme elderly. Our results suggest that clonal expansion in esophageal epithelia is an inevitable consequence of normal aging, differentially impacting the development of cancer depending on mutation type and exposure to drinking and smoking.

  Study EGAS00001003008

• Prostate_Cancer_Whole_Genome_Validations

  We propose to definitively characterise the somatic genetics of Prostate cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing. This study will aim to validate the findings of the whole genome study by re-sequencing regions of interest using a bespoke pulldown bait. See ICGC website for more information: http://icgc.org/icgc/cgp/70/508/71331

  Study EGAS00001000427

• SCAT_osteosarcoma_sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 osteosarcoma cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes

  Study EGAS00001000196

• Whole Exome Sequencing of High grade T1 non-muscle invasive bladder cancer

  High-grade T1 (HGT1) bladder cancer (BC) is the highest risk subtype of non-muscle-invasive BC with unpredictable outcome and poorly understood risk factors. Here we performed whole exome sequencing across 61 HGT1 samples to identify genomic predictors of good outcome, recurrence or progression. This study includes somatic mutation calls and clinical data for 61 HGT1 tumors.

  Study EGAS00001004603

• 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

• A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer (D-Beyond)

  This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.

  Dataset EGAD00001004391

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

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

  Dataset EGAD00001001963

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

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

  Dataset EGAD00001001964

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

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

  Dataset EGAD00001001969

• Genome and transcriptome sequence data from a melanoma skin cancer - squamous cell carcinoma patient

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

  Dataset EGAD00001002018

• Genome and transcriptome sequence data from a metastatic small cell carcinoma of unknown primary cancer patient

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

  Dataset EGAD00001002641

• Spatial targeted gene sequencing of metastatic melanoma

  We performed deep targeted DNA sequencing for a panel of 265 cancer-related genes. This included subsampling 35 different regions of a metastatic melanoma biopsy that was treated with anti-PD-1 inhibitor. Samples with cancer cell purity greater than 80% based on pathologic assessment were used for cancer gene panel DNA sequencing. Mean sequencing coverage was 861x and paired-end reads in FASTQ format were generated by the Illumina pipeline and aligned to the reference human genome hg19 build using the Burrows-Wheeler Alignment Tool (BWA, v0.7.5) with default settings. Aligned reads were further processed using GATK with best practices for removing duplicates, indel removal and recalibration.

  Dataset EGAD00001005821

• Sequencing cancer mutations in various types of lung cancer using the long-read, portable sequencer

  In this study, we used a long-read and portable sequencer MinION to identify cancer mutations in lung adenocarcinoma cells. We performed cDNA amplicon sequencing for various types of mutations such as point mutations in EGFR and KRAS and oncogenic fusion transcripts in ALK and RET. Using the long reads of MinION, we also conducted mutation phasing of EGFR TKI-sensitive and resistant mutations, which would provide useful information to next thrapeutic approaches for cancers. We applied this method to identify mutation genotypes of eight clinical samples from Japanese lung adenocarcinomas. This method could provide new sequencing-based diagnostic approaches for lung cancers. Additinally we also performed cancer mutation identification of risk-dependent unique samples. Usual interstitial pneumonia (UIP) is a risk factor for lung carcinogenesis. This study was performed to characterize mutagenesis and mutational target genes underlying lung carcinogenesis in patients with UIP.We performed whole exome sequencing of lung adenocarcinoma with usual interstitial pneumonia.

  Study JGAS000065

• TONIC-Trial-cfDNA-Project

  Cell-free DNA (cfDNA) is an emerging technology to predict and monitor response to cancer treatment, including immune checkpoint blockade (ICB). However, data on cfDNA dynamics during ICB in metastatic triple negative breast cancer (mTNBC) are limited. While most applications of cfDNA involve assays that focus on mutation detection, mTNBC and multiple other cancer types are driven by copy number alterations (CNAs). We evaluate cfDNA-based copy number profile abnormality (CPA) score as a potential biomarker for monitoring ICB response in mTNBC, analyzing data from 87 patients enrolled in stage 1 and stage 2 of the TONIC-trial. We find significant concordance between cfDNA-based and tissue-based CNA profiles. Additionally, responders show a decrease in CPA scores upon ICB at week 6 (3 cycles of nivolumab). These findings underscore the potential of cfDNA-based CNA dynamics as a non-invasive biomarker for ICB early response assessment in patients with mTNBC.

  Study EGAS50000001308

• Colon cancer targeted sequencing study contaning WBCs, primary tumor tissue and plasma samples

  In the setting of localized colon cancer (CC), circulating tumor DNA (ctDNA) monitoring in plasma has shown potential for detecting minimal residual disease (MRD) and predicting higher risk of recurrence. With the tumor-only sequencing approach, however, germline variants may be misidentified as somatic variations, precluding the possibility of tracking in up to 11% of patients due to a lack of known somatic mutations. In this study comprising 148 prospectively recruited localized CC patients, a custom 29-gene panel was utilized to sequence both tumor tissue and matched white blood cells (WBCs) to enhance the accuracy of sequencing results. Performing targeted sequencing of paired tumor tissue and WBCs samples detected additional somatic mutations and increased the number of patients eligible for MRD tracking in plasma, although MRD detection sensitivity was not increased. Furthermore, the germline testing approach revealed the presence of pathogenic germline variants, thereby helping identify patients at elevated risk of hereditary cancer syndromes.

  Study EGAS50000000059

• A Genomics-Based Classification of Human Lung Tumors

  We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.

  Study EGAS00001000647

• Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer

  Mismatch repair (MMR) deficient cancer evolves through the continuous erosion of coding homopolymers in target genes. Curiously, the MMR genes MSH6 and MSH3 also contain coding homopolymers and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient colorectal cancer evolution is unknown. We show that microsatellite instability modulates DNA repair by toggling hypermutable mononucleotide homopolymer runs in MSH6 and MSH3 through stochastic frameshift switching. Spontaneous mutation and reversion modulates subclonal mutation rate, mutation bias, and clonal HLA and neoantigen diversity. Patient-derived organoids corroborate these observations and show that in the absence of immune selection MMR homopolymer sequences drift back into reading frame, suggesting a fitness cost of elevated mutation rates. Combined experimental and simulation studies demonstrate that subclonal immune selection favours incremental MMR mutations. Overall, our data demonstrate that MMR-deficient colorectal cancers fuel intratumour heterogeneity by adapting subclonal mutation rate and diversity to immune selection.

  Study EGAS50000000297

• Spatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases

  Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis, yet our understanding of tumor microenvironmental (TME) characteristics associated with GCPM remain limited. Here, we analyzed intrinsic genomic alterations and transcriptomic programs predictive of GCPM in a prospective cohort of 248 patients, identifying CDH1, PIGR, and ELF3 mutations as predictors. By inspecting the spatial dynamics of the TME, we find that tumor compartment infiltration of pro-tumorigenic cell types such as inflammatory cancer-associated fibroblasts (CAFs) predict peritoneal recurrence. Next, in a cross-sectional study of 205 samples from 55 patients, distinct pathways and immune compositions in GCPM relative to liver metastases highlight the TME's significance in transcoelomic metastases. Notably, several putative therapeutic targets exhibited distinct expression patterns between PTs and PMs. Our findings highlight transcriptomic variations and niche reprogramming in the GCPM peritoneal environment, revealing roles of myeloid dendritic cells, effector memory CD8+ T cells, and CAFs in metastatic progression.

  Study EGAS50000000501

• Epstein-Barr Virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review

  This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with especially the EBV-negative area showing more complex DNA aberrations, reminiscent of Chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlighting the impact of EBV loss on tumour behaviour.

  Study EGAS50000000706

• whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases

  Esophageal cancer is one of the most aggressive cancers and the sixth leading cause of cancer death worldwide1. Approximately 70% of the global esophageal cancers occur in China and over 90% histopathological forms of this disease are esophageal squamous cell carcinoma (ESCC)2-3. Currently, there are limited clinical approaches for early diagnosis and treatment for ESCC, resulting in a 10% 5-year survival rate for the patients. Meanwhile, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we show a comprehensive genomic analysis in 158 ESCC cases, as part of the International Cancer Genome Consortium (ICGC) Research Projects (http://icgc.org/icgc/cgp/72/371/1001734). We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases and additional 70 ESCC cases were subjected to array comparative genomic hybridization (a-CGH) analysis.

  Study EGAS00001000709

• Characterization and clinical relevance of the genomic alterations defining invasive lobular breast cancer

  Background: Invasive lobular breast cancer (ILBC) is the second most common histological subtype after ductal breast cancer (IDBC). In spite of significant clinical and pathological differences, ILBC is still treated as IDBC. Here, we aimed at identifying recurrent genomic alterations in ILBC with potential clinical implications.Methods: Starting from 630 ILBC primary tumors with a median follow up of 10 years, we interrogated oncogenic substitutions and indels of 360 cancer genes and genome-wide copy number alterations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinical, pathological, and outcome features. The Cancer Genome Atlas database was used for comparison of frequency estimates.Results: Besides the high mutation frequency of CDH1 in 65% of the tumors, alterations in one of the three key genes of the PI3K pathway, PIK3CA, PTEN and AKT1, were present in more than half of the cases. ERBB2 and ERBB3 were mutated in 5.1 and 3.6% of the tumors. FOXA1 mutations and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than IDBC. The histological diversity of ILBC was associated with specific genomic alterations, such as enrichment for ERBB2 mutations in the mixed, non-classic subtype, and for ARID1A mutations and ESR1 gains in the solid subtype. Finally, ERBB2 and AKT1 mutations were associated with short-term risk of relapse, and chromosome 1q and 11p gain with increased and decreased breast cancer free survival, respectively.Conclusion: ERBB2, ERBB3 and AKT1 mutations represent high prevalence therapeutic targets in ILBC. FOXA1 mutations and ESR1 gains urgently deserve dedicated clinical investigation, especially in the context of endocrine treatment.

  Dataset EGAD00001001395

• Norwegian Institute of Public Health – Cancer Registry of Norway Data Access Policy for JanusRNA transcriptomics datasets archived in Federated EGA Norway

  JanusRNA transcriptomics datasets are generated from biobank samples from the Janus Serum bank of the Cancer Registry of Norway/National Institute of Public Health. This Data Access Committee has been appointed to govern controlled access to these datasets archived in Federated EGA Norway.

  Dac EGAC50000000192

• DAC for EGA study: Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer

  This is the Data Access Committee for the EGA study: Multi-omic analyses from a randomized phase II study of epigenetic priming followed by nivolumab in previously treated metastatic non-small cell lung cancer (temp ID 800).

  Dac EGAC50000000563

• Whole genome sequence analysis in patients with primary central nervous system lymphomas

  We performed target amplicon sequencing analysis in 28 patients with primary central nervous system lymphomas using target capture technology (NGS) on Cancer Panel to explore molecular targets.

  Study JGAS000258

• Colon adenomas and adenocarcinomas and matched mucosae

  Whole exome sequencing in sporadic colorectal cancers (CRC) and advanced adenomas (Ad-As), and their paired healthy mucosa, for a deeper understanding of the biology of this cancer.

  Study EGAS00001007255

• ACUITI

  This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in patients with metastatic HR+/HER2- breast cancer receiving endocrine therapy and CDK4/6 inhibitors.

  Study EGAS50000000962

• Clinical and molecular features of early onset pancreatic cancer

  A retrospective cohort study on the clinical and molecular features of early onset pancreatic cancers (i. e. diagnosed at <50 years old) in comparison with later onset tumors.

  Study EGAS50000000362

• Prediction of HLA genotypes using NGS data

  High-precision human leukocyte antigen (HLA) genotyping is crucial for anti-cancer immunotherapy, but existing tools predicting HLA genotypes using next-generation sequencing (NGS) data are insufficiently accurate.

  Study EGAS00001005274

• Ovarian Cancer Single Cell Whole Genome Sequencing

  Five primary, treatment-naive ovarian cancer specimens were subjected to single cell whole genome sequencing (10x Genomics workflow). Libraries were sequenced on an Illumina NovaSeq 6000 instrument. Sequencing data was processed with the Cell Ranger DNA pipelines. Archived here are BAM files for each sample.

  Dataset EGAD50000002102

• Sequencing dataset for the Predictive Endocrine ResistanCe Index (PERCI) in Breast Cancer cases

  Sequencing dataset for the Predictive Endocrine ResistanCe Index (PERCI) in Breast Cancer cases of the WSG-ADAPT trial (NCT01779206). The Oncomine Comprehensive v3 assay (ThermoFisher) and a customized amplicon-based NGS-Panel (DERv2) was performed.

  Dataset EGAD50000001595

• Breast Cancer Sequential Sampling Targeted Capture

  This study aims to target capture sequence regions of interest from DNA derived from breast cancer patients who received neo-adjuvant chemotherapy. All patients had multiple biopsies performed before chemotherapy. Patients who had residual disease after the course of treatment underwent a further biopsy. We aim to characterise the mutations involved.

  Dataset EGAD00001000784

• Reference DNA standards for GCLP pipeline

  The use of reference DNA standards generated from cancer cell lines sequenced in the Cancer Genome Project to establish the sensitivity, specificity, accuracy and reproducibility of the WTSI GCLP sequencing pipeline

  Dataset EGAD00001002015

• A comprehensive characterisation and analysis of human breast cancers through whole-genome sequencing

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

  Dataset EGAD00001002740

• Whole exome sequencing analysis on patient-derived cervical cancer tissues and respective tumoroids

  Whole exome sequencing (WES) was performed on the matched tumor and organoid pairs from 7 cervical cancer patients. The DNA was sequenced on NovaSeq6000 platform with 8Gb sequencing coverage. WES data was mapped against human reference genome GRCh38 by using BWA (v0.7.5) mapping tool.

  Dataset EGAD00001006166

• Copy number profiling of tissue and plasma samples from high grade serous epithelial ovarian cancer patients

  This dataset includes 289 samples from 46 high grade serous epithelial ovarian cancer patients. Data are from both tissue samples (either primary tumor, or synchronous metastases) and circulating cell-free DNA (cfDNA) of plasma samples taken during therapy and follow-up.

  Dataset EGAD00001006422

• Data from Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models

  Data from Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models

  Dataset EGAD00001012228

• 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

• CSER: Exome Sequencing in Diverse Populations in Colorado and Oregon/CHARM Cancer Health Assessments Reaching Many

  The CHARM (Cancer Health Assessment Reaching Many) study, part of the Clinical Sequencing Evidence-Generating Research (CS.ER2) effort, aimed to assess the utility of clinical exome sequencing and how it affects care in diverse populations. The study population included adults at risk for hereditary cancer syndromes. The primary objective was the implementation of a hereditary cancer risk assessment program in healthy 18-49 year-olds in primary care settings within a vertically integrated health delivery system (Kaiser Permanente) and a federal qualified health center (Denver Health). The investigators aimed to assess clinical exome sequencing implementation and interpretation, as well as tailored interactions for low health literacy including a contextualized consent process, and a modified approach to results disclosure and genetic counseling. The investigators were also assessing the clinical utility (healthcare utilization and adherence to recommended care) and personal utility of primary and additional results from clinical exome sequencing, and evaluate the ethical and policy implications of considering personal utility of genomic information decisions for health care coverage.Sequencing and analysis for CHARM was conducted at the Northwest Clinical Genomics Laboratory, University of Washington, Seattle (https://nwgc.gs.washington.edu/).

  Study phs002111

• Global Anaplastic Thyroid Cancer Initiative

  Thyroid cancer is the most common endocrine malignancy. Most thyroid cancers are of the well-differentiated (non-aggressive) phenotype, and are almost always cured with standard treatments. In contrast, anaplastic thyroid cancer (ATC) is rare, accounting for only 1% of thyroid cancers, however it is perhaps the most lethal human malignancy with an average survival of 3 to 6 months. ATC presents with dramatic and rapid onset of airway and esophageal blockage with frequent spread to the lungs. Interestingly, 21–79% of ATCs have coexisting areas or a previous history of well-differentiated cancers. Although this suggests a progression from well-differentiated cancers to ATC, to date there is little molecular conformation that such a progression exists versus de novo generation of ATC. As ATC is extremely rare and most cases are inoperable, there are a paucity of tissue samples for study at any one center. The Global Anaplastic Thyroid Cancer Initiative (GATCI) aims to unite international institutions in order to pool samples (ATC with or without a paired well-differentiated component) for a comprehensive analysis of the genomic landscape of this disease.

  Study EGAS00001002234

• Whole genome and transcriptome analysis of medullary thyroid cancer

  Medullary thyroid cancer is the neoplasm of the calcitonin-producing parafollicular cells of the thyroid gland. The hormone calcitonin acts to lower the blood calcium level, counteracting the effects of the parathyroid hormone; it can also serve as a biomarker for the presence or recurrence of medullary thyroid cancer. Surgery is the only curative treatment for this cancer. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large sub-population of medullary thyroid cancers; however, not all patients carry oncogenic alterations of this kinase. Hence, there is a need for molecular characterization of medullary tumors on the genomic scale with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no therapy options.

  Study EGAS00001001473

• The Ovarian Cancer Association Consortium OncoArray genome-wide association study

  A custom Illumina genotyping array, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis as described in PMID:27697780.The array was used to genotype ovarian cancer cases and controls from multiple studies participating in the Ovarian Cancer Association Consortium, of which 54,747 passes QC.An initial principal components analysis was carried out using a method described in PMID:27697780 to assign subject to intercontinental ancestry groups: “European”, “African”, “Asian” and "Other". Within ancestry principal components analysis was carried using a set of ~33k unlinked markers. Subsequent analyses were adjusted for the ancestry specific PCs: 9 Eur, 10 Asian, 1 African and 6 Mixed. These PCs are included in the imputed dataset phenotypes file

  Study EGAS00001002305

• Systematic dissection of tumor-normal single-cell ecosystems across a thousand tumors of 30 cancer types

  The complexity of the tumor microenvironment poses significant challenges in cancer therapy. Here, to comprehensively investigate the tumor-normal ecosystems, we perform an integrative analysis of 4.9 million single-cell transcriptomes from 1,070 tumor and 493 normal samples in combination with pan-cancer 137 spatial transcriptomics, 8,887 TCGA, and 1,261 checkpoint inhibitor-treated bulk tumors. We define a myriad of cell states constituting the tumor-normal ecosystems and also identify hallmark gene signatures across different cell types and organs. Our atlas characterizes distinctions between inflammatory fibroblasts marked by AKR1C1 or WNT5A in terms of cellular interactions and spatial co-localization patterns. Co-occurrence analysis reveals interferon-enriched community states including tertiary lymphoid structure (TLS) components, which exhibit differential rewiring between tumor, adjacent normal, and healthy normal tissues. The favorable response of interferon-enriched community states to immunotherapy is validated using immunotherapy-treated cancers (n=1,261) including our lung cancer cohort (n=497). Deconvolution of spatial transcriptomes discriminates TLS-enriched from non-enriched cell types among immunotherapy-favorable components. Our systematic dissection of tumor-normal ecosystems provides a deeper understanding of inter- and intra-tumoral heterogeneity.

  Study EGAS50000000324

• BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer

  Checkpoint immunotherapy combined with neoadjuvant chemotherapy improves complete pathologic response in a subset of breast cancer patients. Here, we applied single-cell profiling to tumor biopsies collected before and during anti-PD1 therapy. One-third of tumors exhibited proliferative T-cells expanding along CD8+ or CD4+ lineages, which were either characterized by increased cytotoxicity and exhaustion or improved T-helper function, respectively. Lineage tracing in non-expanding tumors revealed at which point in the lineage T-cells were impaired, while gene expression modeling along these lineages revealed novel genes and underlying transcription factors involved in T-cell expansion. Interestingly, different dendritic and myeloid cell phenotypes could either stimulate or inhibit expanding T-cells, while cell-to-cell communication revealed an integrated immune context highly predictive of T-cell expansion, consisting of immune-stimulatory/-inhibitory interactions between cancer and various immune cell types. Our data yield unprecedented insights into the dynamic changes underlying checkpoint immunotherapy response in breast cancer.

  Study EGAS00001004809

• Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients

  Genome-wide analysis of cell-free DNA (cfDNA) methylation profile has been recognized as a promising approach for sensitive and specific detection of many cancers. However, scaling such genome-wide assays for clinical translation is impractical due to the high cost of whole genome bisulfite sequencing. We have shown that the small fraction of GC-rich genome is highly enriched in CpG sites and disproportionately harbors the majority of cancer-specific methylation signature. Here, we report on the simple but effective Heat enrichment of CpG-rich regions for Bisulfite Sequencing (Heatrich-BS) platform that allows for focused methylation profiling in these highly informative regions. Our novel method and bioinformatics algorithm enable accurate tumor burden estimation with high sensitivity and quantitative tracking of colorectal cancer patient’s response to treatment, at much reduced sequencing cost suitable for frequent monitoring. We also show, for the first time, tumor epigenetic subtyping from cfDNA using Heatrich-BS, which could enable patient stratification from non-invasive liquid biopsy. As such, Heatrich-BS holds great potential for highly scalable screening and regular monitoring of cancer using liquid biopsy.

  Study EGAS00001006198

• Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer

  Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identified five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reasoned that their strong selection should prioritise them as key biomarkers for targeted therapies. We used primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number was associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC was statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway was independently observed in squamous lung cancer and triple negative breast cancer. These results suggest that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.

  Study EGAS00001006200

• DNA methylation landscape of prostate cancer

  Metastases from primary prostate cancers to rare locations, such as the brain, are becoming more common due to longer life expectancy thanks to improved treatments. Epigenetic dysregulation is a feature of primary prostate cancer, and distinct DNA methylation profiles are associated with the mutually exclusive SPOP mutant or TMPRSS2-ERG fusion genetic backgrounds. Using a cohort of 42 patients with prostate cancer brain metastases (PCBM), with matched primary samples available for 17 patients, we carried out DNA methylation analysis using Illumina EPIC array. We examined the epigenetic distinction between primary PCa and PCBM, the association between epigenetic alterations and mutational background, and particular epigenetic alterations that may be associated with PCBM in particular. Multiregion sampling of PCBM revealed epigenetic heterogeneity in metastases. We found aberrant methylation in PCBM is associated with mutational background, PRC2 complex activity and upregulation of EZH2, an effect that is particularly pronounced in SPOP mutant PCBM. While we detected a hypermethylator phenotype in PCBM, we also observed hypomethylation occurring at the promoters of genes involved in neuroactive ligand-receptor interactions or the calcium signalling pathway, such as GABRB3 and GRM5, a change not observed in non-brain prostate cancer metastases.

  Study EGAS00001006670

• Single-Cell DNA and RNA Sequencing over A 29-Year Period of A CLL Patient Demonstrating Evolution of Multiple Cell Clones

  Chronic lymphocytic leukemia (CLL) is a frequent B-cell malignancy characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single nucleotide polymorphism (SNP) microarray analyses of a single CLL patient over 29-years of observation and treatment, and transcriptome and whole genome sequencing at selected timepoints. We identified chromosome alterations of 13q14-, 6q- and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and a chromosome 10 copy neutral loss of heterogeneity (LOH) that marks a major population dominant at death. Serial single cell RNA sequencing revealed elevated mRNA expression of the FOS, JUN and KLF4 genes just before the appearance of acute disease requiring therapy. This gene expression pattern became undetectable following therapy, but reoccurred following relapse. Transcriptome evolution indicates that complex expression changes occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy.

  Study phs001181

• CD4+ cell transcriptional profiling by RNA sequencing

  We use next generation sequencing to investigate the different transcriptomes of closely related CD4+ T-cells from healthy human donors to elucidate the genetic programs that underlie their specialized immune functions. Six cell types were included: Regulatory T-cells (CD25hiCD127low/neg with &#62;95% FOXP3+ purity), regulatory T-cells activated using PMA/ionomycin, CD25-CD45RA+ (&#39;naive&#39; helper T-cells), CD25-CD45RO+ (&#39;memory&#39; helper T-cells), activated Th17 cells (&#62;98% IL17A+ purity) and activated IL17-CD4+ T-cells (called &#39;ThPI&#39;). Poly-T capture beads were used to isolate mRNA from total RNA, and fragment sizes of ~200 were sequenced from both ends on Illumina&#39;s genome analyzer. We confirm many of the canonical signature genes of T-cell populations, but also discover new genes whose expression is limited to specific CD4 T-cell lineages, including long non-coding RNAs. Additionally, we find that genes encoded at loci linked to multiple human autoimmune diseases are enriched for preferential expression upon T-cell activation, suggesting that an aberrant response to T-cell activation is fundamental to pathogenesis.

  Study phs000626

• Genetics of Glucose Regulation in Gestation and Growth (Gen3G) Cohort - Placenta Transcriptomics RNA Sequencing

  The overarching goals of Genetics of Glucose regulation in Gestation and Growth (Gen3G) are to increase our understanding of biological, environmental, and genetic determinants of glucose regulation during pregnancy and their impact on fetal/child development. Gen3G is a prospective cohort study: we initially recruited 1,024 pregnant women between 2010-2013 at Blood Sampling in Pregnancy Clinic during the first trimester of pregnancy (median 9 weeks of gestation) in Sherbrooke, Qu&#233;bec, Canada. We assessed 898 pregnant women at second trimester (median 26 weeks of gestation), when participants completed a 75g oral glucose tolerance test (OGTT) as clinically indicated for screening of gestational diabetes mellitus (GDM). We collected data for 854 mother-child dyads at delivery (from medical records), in addition to placenta and/or cord blood samples in majority of newborns.The overall goal of the grant that supported data that is included in this dbGaP submission was to discover novel placental factors that regulate glucose metabolism in pregnancy and predict GDM by conducting genome-wide transcriptomics (RNA and miRNA) in carefully collected placenta samples from Gen3G.

  Study phs003151

• RTEL1 mutation as a modifier of Dyskeratosis Congenita in a family with a Telomerase RNA (hTR) template mutation and variant telomeric repeats

  Vertebrate telomeres, the sequences protecting the end of linear chromosomes, are composed of conserved hexameric GGTTAG repeats. Here we present a C50>A telomerase RNA template mutation that results in the incorporation of the variant telomeric repeat GTTTAG in a family with dyskeratosis congenita primarily presenting as idiopathic pulmonary fibrosis. The mutant telomerase is characterized by decreased processivity in direct telomerase activity assays and in vivo based on data from Illumina next-generation whole genome sequencing and Oxford Nanopore Technologies long-read telomere sequencing. The latter provided positional mutant repeat information that revealed the inheritance and maintenance of proximal mutant repeats in individuals who did not inherit the template mutation. Additionally, we describe an RTEL1 nonsense mutation that is associated with very short telomeres in progeny harboring wild-type telomerase and inherited mutant telomeric repeats in the absence of overt clinical phenotypes. In contrast, co-inheritance of the RTEL1 nonsense and TERC r.C50>A mutations coincided with severe early-onset DC phenotypes in two individuals.

  Study EGAS50000001644

• Molecular Determinants of Tumor Behavior in Early Lung Adenocarcinoma

  Lung adenocarcinoma is the leading cause of cancer death worldwide and a heterogeneous disease with poor survival in the advanced stage. Given that the frequency of early diagnosis is increasing, the investigation of the molecular determinants of disease progression is paramount. Prediction of whether the tumor is indolent or aggressive has been the subject of recent investigations. Yet, the molecular underpinnings explaining the difference in tumor behavior remains largely unknown and is directly relevant to the efficacy and cost-effectiveness of lung cancer screening, including the risks of over-diagnosis and overtreatment. To gain insights into the molecular pathogenesis and the underlying molecular determinants of clinical behavior of early adenocarcinoma, we investigated genetic alterations in 102 surgically resected early adenocarcinomas. We hypothesized that the behavior of early adenocarcinoma can be predicted based on genomic underpinnings. To identify the type of genomic alterations associated with resected indolent and aggressive early lung ADC, the DNA samples from 21 adenocarcinoma in situ (AIS), 27 minimally invasive adenocarcinoma (MIA) and 54 fully invasive adenocarcinoma were collected and subjected to a deep next generation sequencing, targeting a custom 347 cancer gene panel. Our study provides new insights into cancer genomic evolution, helps to elucidate the interplay of somatic mutation and the adaptation of clones, and brings new insights into the key distinction between indolent and aggressive tumor behavior.

  Study phs001811

• This study generated Oxford Nanopore long read sequencing data of cancer cell line mixtures for validating long-read variant calls in cancer genomics

  Long-read sequencing (LRS) improves genome alignment and facilitates resolving variants in complex genomic regions, making it a promising approach for cancer variant detection and biomarker discovery. Here, we evaluate the performance of LRS to detect somatic variants across different tumour purities and sequencing depths by comparing to somatic variants from short-read sequencing. We generated experimental mixtures of cancer cell lines and matched normal cell lines to simulate 10 tumour purities (ranging from 0 to 100% tumour content). This resulted in 22 samples which were sequenced using whole genome LRS to a targeted depth of 60x and somatic variants were identified. We downsampled sequencing data to explore the optimal read depth for somatic variant detection. Our results show that long-read variant calling tools achieve recall rates comparable to short-read gold standards. While a tumour sequencing depth of 30x to 60× is generally sufficient for detecting common variants, particularly structural variants (SVs), sequencing the matched normal sample at adequate depth is crucial for accuracy. Notably, we found variants unique to LRS that may represent real and previously undetected events. This study highlights key factors for optimising cancer genome sequencing with LRS and provides a comprehensive dataset of cell line mixtures for future research and tool development.

  Study EGAS00001008107

• Defined Lifestyle and Germline Factors Predispose Asian Populations to Gastric Cancer

  Gastric cancer (GC) is one of the leading causes of cancer mortality throughout the world, with the highest incidence in east-Asia. Although the somatic genetics of GC has extensively been characterized by recent advances in cancer genome sequencing, the germline and environmental effects on GC and their ethnic differences have poorly been understood. Here, we performed genomic scale trans-ethnic analysis of 531 GC cases (319 Asian and 212 non-Asians), by integrating east-Asian and public GC datasets. There is one distinct GC subclass with clear alcohol-associated mutation signature and strong Asian specificity, and almost all the cases in the subclass are attributable to alcohol intake behavior, smoking habit, and Asian-specific ALDH2 defective allele. Alcohol-related GCs have low mutation burden and a characteristic immune profile of increased B-cell infiltration into the tumor area in relation to cancer cell-intrinsic CXCL13 chemokine expression. In addition to germline variants of genes involved in BRCA pathways, we found frequent (7.4%) germline CDH1 variants among Japanese GCs. Most of them were attributed to a few recurrent SNVs shared by both Japanese and Koreans, suggesting the existence of common ancestral events and widespread distributions of these pathogenic variants among east-Asian populations. Specifically, approximately one-fifth of diffuse-type GCs were attributable to the combination of alcohol intake and defective-ALDH2 allele or to germline CDH1 variants. These results revealed uncharacterized impacts of germline variants and their interplays with lifestyles in the high incidence areas.

  Study JGAS000229

• Defined Lifestyle and Germline Factors Predispose Asian Populations to Gastric Cancer

  Gastric cancer (GC) is one of the leading causes of cancer mortality throughout the world, with the highest incidence in east-Asia. Although the somatic genetics of GC has extensively been characterized by recent advances in cancer genome sequencing, the germline and environmental effects on GC and their ethnic differences have poorly been understood. Here, we performed genomic scale trans-ethnic analysis of 531 GC cases (319 Asian and 212 non-Asians), by integrating east-Asian and public GC datasets. There is one distinct GC subclass with clear alcohol-associated mutation signature and strong Asian specificity, and almost all the cases in the subclass are attributable to alcohol intake behavior, smoking habit, and Asian-specific ALDH2 defective allele. Alcohol-related GCs have low mutation burden and a characteristic immune profile of increased B-cell infiltration into the tumor area in relation to cancer cell-intrinsic CXCL13 chemokine expression. In addition to germline variants of genes involved in BRCA pathways, we found frequent (7.4%) germline CDH1 variants among Japanese GCs. Most of them were attributed to a few recurrent SNVs shared by both Japanese and Koreans, suggesting the existence of common ancestral events and widespread distributions of these pathogenic variants among east-Asian populations. Specifically, approximately one-fifth of diffuse-type GCs were attributable to the combination of alcohol intake and defective-ALDH2 allele or to germline CDH1 variants. These results revealed uncharacterized impacts of germline variants and their interplays with lifestyles in the high incidence areas.

  Study JGAS000228

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

  Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR]=0.3 in the targeted sequencing and OR=0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR=6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, nonresponding tumors with initially small sizes carried a higher risk of recurrence. These findings offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

  Study EGAS00001007501

• Hangzhou Cancer study

  Dac EGAC00001000765

• Singapore gastric cancer WGS

  Dac EGAC00001000888

• Colorectal cancer samples

  Dac EGAC00001002808

• Leeds Cancer Genomics

  Dac EGAC00001003010

• Brain Cancer Center Committee

  Dac EGAC00001003523

• IBD-dysplasia

  Study EGAS00001003767

• GCP study

  Study EGAS00001004959

• Diverse Cellular Composition in Alveolar Rhabdomyosarcoma Revealed by Single Cell RNA Sequencing

  Using single cell RNAseq data to characterize tumor composition and cellular states for Alveolar Rhabdomyosarcoma. We find that that ARMS tumors harbor phenotypically and transcriptionally distinct malignant subpopulations within an immune-influenced microenvironment.

  Study EGAS50000001564

• A single-cell atlas of meningioma

  To explore meningioma intra-tumoral heterogeneity at scale, we generated the largest cohort profiled to date with single-nuclear RNA sequencing (snRNAseq, n = 102 samples and 580,185 high-quality nuclei) as well as high-resolution spatial transcriptomics (Visium HD, n = 43 samples and 7,146,538 115 segmented cells).

  Dataset EGAD50000002272

• This dataset contains the Fastq files from the RNA sequencing

  Whole blood was stimulated Ex vivo with Heat Killed M abscessus and M haemophilum or left untreated with Saline for each individual Healthy Control and MH-infected participants

  Dataset EGAD50000001566

• 10X Genomics single-nuclei RNA-sequencing of endometrium from women with and without PCOS

  Chromium Next GEM Single Cell 3’ Gel Bead Kit (Dual Index) v3.1 (10X Genomics) of endometrium from 27 women including 5 without PCOS and 12 with PCOS. Following baseline biopsies, PCOS participants underwent a 16-week randomized controlled trial with metformin (n=7) or lifestyle intervention (n=3). 25,000 raw reads per nucleus

  Dataset EGAD50000001017

• Single-sell RNA sequencing counts from 7 acute myeloid leukemia patients and 3 healthy donors

  This dataset contains count data (from 10X CellRanger) and metadata from 7 acute myeloid leukemia subjects treated with chemotherapy, as well as data from 3 healthy donors. Additionally, the dataset includes VDJ data for all subjects except for 31_base and the 3 healthy donors (TCRseq not performed).

  Dataset EGAD50000000525

• Tomoseq data set

  This object contains raw FATSq files and processed files of the sections of an entire EMD lesions of patient PT01A and PT10. The raw files represent bulk RNA sequencing of each of the sections. The processed file is a CSV file that contains gene expression.

  Dataset EGAD50000000335

• Short-read single-cell RNA-sequencing of the human brain in neurodegenerative diseases

  Nuclei were isolated from postmortem human brain tissue, and single-nucleus barcoded cDNA libraries were generated using the 10X Genomics 3' v3.1 kit. Samples were sequenced on an Illumina NovaSeq 6000 to an average of 343 million reads per sample and 52,000 reads per cell.

  Dataset EGAD50000000178

• nanostring_gene_expression

  Two to four sections of 10 µm thickness each (depending on sample size) from the respective formalin-fixed paraffin-embedded (FFPE) tissue sample were used for RNA isolation on 46 resected tumors as well as 17 paired biopsies. Digital gene expression analysis was performed on the NanoString nCounter platform, utilizing the NanoString MAX/FLEX system, with the PanCancer Immune Profiling panel as well as the PanCancer Pathway panel provided by NanoString.

  Dataset EGAD00010002654

• Tcells_CD_scRNAseq

  This set features unfiltered, aligned, UMI-based single cell RNA sequencing count data for 5290 Blood, intraepithelial ileum (IEL) and lamina propria ileum (LPL) T cells from Crohn's disease patients as published in Uniken Venema et al, Gastroenterology 2019

  Dataset EGAD00010001649

• Sequencing data for oesophageal and related samples - OACs release 1 (RNA)

  Dataset EGAD00001002259

• Glioblastoma CRISPR Screen (2017-04-27)

  This is an in vitro genome-wide CRISPR/cas9 screen in human glioblastoma stem cells, screening for genes essential for survival of these cells. These cells express cas9 and have been transfected with a guide RNA library causing gene knockouts. We will analyse the sequencing data for depletion of guide RNAs. This dataset contains all the data available for this study on 2017-04-27.

  Dataset EGAD00001003308

• Capture Hi-C on Hodgkin lymphoma

  In situ promoter capture Hi-C on Hodgkin lymphoma cell line L-428 in experimental triplicates. Hi-C libraries were prepared as previously described (Orlando et al., 2018, https://currentprotocols.onlinelibrary.wiley.com/doi/pdf/10.1002/cphg.63). Promoter capture was based on 32,313 biotinylated 120-mer RNA baits (Agilent). Hi-C libraries were sequenced using Illumina HiSeq 2000 technology. The files are in FASTQ format.

  Dataset EGAD00001004321

• POT1 splice site mutant analysis

  We are interested in the contribution mutations in the Shelterin complex protein POT1 may have to the development of melanoma. We have identified a patient who carries a splice site mutation in POT1 and as part of our analysis of this gene we aim to sequence the transcriptome of this patient to see how this mutation influences splicing. RNA has been obtained from lymphocytes collected from the patient.

  Dataset EGAD00001000786

• Glioblastoma CRISPR Screen (2016-06-02)

  This is an in vitro genome-wide CRISPR/cas9 screen in human glioblastoma stem cells, screening for genes essential for survival of these cells. These cells express cas9 and have been transfected with a guide RNA library causing gene knockouts. We will analyse the sequencing data for depletion of guide RNAs. This dataset contains all the data available for this study on 2016-06-02.

  Dataset EGAD00001002158

• TTV018 RORC IBD-associated genotype effects on RORgT expression and function in ex vivo T cells

  RNA sequencing of peripheral immune cells from patients +/- an IBD risk variant. Peripheral immune cells +/- in vitro test compound treatment. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001002233

• SARS-CoV2 nasal epithelium

  Single cell RNA sequence generated from human primary nasal epithelium differentiated at air-liquid interface. This dataset comprises tissue from two donors, with cultures either unexposed or exposed to SARS-CoV2. Libraries were prepared using the 10X Genomics pipeline as per manufacturer's instructions.

  Dataset EGAD00001008159

• Single cell atlas of human glioma

  We profiled 87 primary-recurrentpatient-matched paired GBM specimens with single-nucleus RNA and bulk-DNA sequencing and single-cell open-chromatin and spatial transcriptomics/proteomics assays. We found that recurrent GBMs are characterized by a shift to a mesenchymal phenotype in response to therapy

  Dataset EGAD00001008811

• RNAseq before and after cold pressor test

  The cold pressor test (CPT) is a widely used pain provocation test to investigate both pain tolerance and cardiovascular responses. Twenty-two females were phenotypically assessed before and after a CPT, and blood samples were taken for RNA-sequencing. Files were processed and quantified with kallisto v0.42.5 using the human reference transcriptome (Gencode Release 28). Countdata was rlog-transformed.

  Dataset EGAD00001009649

• Long read mRNA sequencing of blood cells exposed to different immune stimuli

  Long-read (PacBio) RNA sequencing dataset of in vitro stimulated PBMC cells. 5 samples consisting of 1 RPMI control and 4 stimulus conditions (lipopolysaccharide (LPS), polyI-polyC, S. aureus and C. albicans) all originating from one donor. Files are raw BAM format files generated by Sequel 2 machine.

  Dataset EGAD00001009998

• SMARTer bulk RNA sequencing for highly purified CD271+ BMSCs from NBM and AML

  bulk RNAseq was conducted on highly purified CD45 - CD71 - CD235a - CD31 - CD271 + BMSCs isolated from a cohort of newly diagnosed 62 AML patients, uniformly treated within an intensive chemotherapy clinical trial and selected to represent the mutational landscape of AML

  Dataset EGAD00001011056

• bulk RNA-seq: A Cultured Leukemia Stem Cell Model Enables Validation of CDK6 as a Stemness Target Against Acute Myeloid Leukemia

  Acute myeloid leukemia (AML) represents a group of aggressive hematological malignancies, the clinical management of which is made challenging due to the persistence of rare and therapy resistant leukemia stem cells (LSCs) which serve as a source of disease relapse and poor outcomes. There are currently a paucity of methods to reliably enrich and study LSCs, hindering the development of therapies that specifically target LSCs. In this study, we deeply characterize the OCI-AML8227 culture model, which maintains a functional stemness hierarchy originating from its highly primitive CD34⁺CD38⁻ cells, to elucidate LSC biology and uncover LSC-specific therapeutic vulnerabilities. We analyzed both bulk and single-cell proteomics, transcriptomics, and epigenomics to generate a LSC protein-protein interaction network, which was then integrated with an LSC-focused small molecule screen using this model. From these findings, CDK6 was discovered as a therapeutic vulnerability specific to LSCs, which was validated in findings from the BEAT-AML cohort and a patient-derived xenograft (PDX) panel of AML samples through palbociclib treatment. Taken together, our studies validate CDK6 as a druggable vulnerability in LSCs, and authenticate OCI-AML8227 cells as a LSC target discovery engine.

  Study EGAS50000000789

• Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities RNA-Seq

  Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.

  Study EGAS00001006866

• A Pilot Study Using Next Generation Sequencing in Advanced Cancers: Feasibility and Challenges

  In this study, we used NGS to identify somatic events in advanced stage cancer patients to demonstrate the feasibility for using this approach to improve patient treatment.

  Study phs000657