Search Results - EGA European Genome-Phenome Archive

Conserved interferon-gamma signaling and decreased immune exclusion programs in responses to immune checkpoint blockade therapy_CM38-RNA

We analyzed baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). Analysis of whole transcriptome data showed that T cell infiltration and interferon-gamma signaling signatures corresponded most highly with clinical response to therapy, with a reciprocal decrease in cell cycle and WNT signaling pathways in responding biopsies. Clinical outcome differences were likely not due to differential melanoma cell responses to interferon-gamma, as 57 human melanoma cell lines exposed in vitro to this cytokine showed a conserved interferon-gamma transcriptome response unless they had mutations that precluded signaling from the interferon-gamma receptor. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream interferon-gamma signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.

Dataset EGAD00001006282

Conserved interferon-gamma signaling and decreased immune exclusion programs in responses to immune checkpoint blockade therapy_CM38-DNA

We analyzed baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). Analysis of whole transcriptome data showed that T cell infiltration and interferon-gamma signaling signatures corresponded most highly with clinical response to therapy, with a reciprocal decrease in cell cycle and WNT signaling pathways in responding biopsies. Clinical outcome differences were likely not due to differential melanoma cell responses to interferon-gamma, as 57 human melanoma cell lines exposed in vitro to this cytokine showed a conserved interferon-gamma transcriptome response unless they had mutations that precluded signaling from the interferon-gamma receptor. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream interferon-gamma signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.

Dataset EGAD00001006284

Epigenetic subtypes of neuroblastoma - ChIPseq

In the absence of recurrent gene mutations, evidence accumulates that epigenetic deregulation plays a prominent role in neuroblastoma biology. Here we provide genome wide H3K27ac profiles in 60 primary neuroblastoma samples.

Dataset EGAD00001006285

Epigenetic subtypes of neuroblastoma - RNAseq

In the absence of recurrent gene mutations, evidence accumulates that epigenetic deregulation plays a prominent role in neuroblastoma biology. Here we provide RNAseq profiles in 71 primary and relapse neuroblastoma samples.

Dataset EGAD00001006286

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients with Advanced Lung Adenocarcinoma

NGS data of 12 patients enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017.

Dataset EGAD00001006287

ctDNA monitoring using patient-specific sequencing and integration of variant reads - Breast cohort

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

Dataset EGAD00001006293

Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma

Whole genome sequencing data of isogenic ATRX/TP53 knockout clones of the neuroblastoma cell line SK-N-SH

Dataset EGAD00001006294

Genomic and transcriptomic data of glioma specimens

Dataset consists of 207 glioma samples of WHO grades II, III and IV. Dataset consists 182 tumor derived genomic data of ~700 cancer-related and epigenetic-related genes with matched blood samples for 48 specimens. Dataset also consists transcriptomic data for 105 specimens. In total 335 bam files were deposited.

Dataset EGAD00001006299

Genomic characterization (through whole-exome sequencing) of bone marrow clonal plasma cells before and after VRD treatment from multiple myeloma patients.

WES data from clonal pahtologic bone marrow plasma cells of multiple myeloma patients. From each patient there are three samples, pathologyc bone marrow plasma cells at diagnosis, pathologyc bone marrow plasma cells after VRD treatment and T lymphocytes as germline control. There are 14 patients in total

Dataset EGAD00001006302

The Transcriptional Landscape of SHH Medulloblastoma

To further understand the biology of Sonic hedgehog medulloblastoma and its molecular subtypes, we studied 250 human Shh-MB using strand-specific RNA sequencing. We identified novel alterations within the cAMP dependent pathway and found that 18% of tumors have genetic events that directly target the abundance and/or stability of MYCN. We also discovered an extensive network of fusions in focally amplified regions, and several loss-of-function fusions in tumor suppressor genes PTCH, SUFU and NCOR1. Molecular convergence on a core of specific genes by nucleotide variants, copy number aberrations, and gene fusions highlights key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma.

Dataset EGAD00001006305

Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma_CM67-RNASeq

Purpose Exploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma. Patients and Methods Patients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS. Results In the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (> median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature. Conclusions Combined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.

Dataset EGAD00001006306

Glioblastoma stem cell lines WGS data

WGS data for 20 Glioblastoma stem cell (GSC) lines and matched blood samples. Fastq files are available. For 10 GSC samples and the 10 matched blood samples the reads are on 3 fastq files per sample

Dataset EGAD00001006488

Low Coverage Whole Genome Sequencing from high grade osteosarcoma

This dataset contains the WGS of 35 samples (high grade osteosarcoma). All cases were reviewed by an expert bone pathologist and have a tumour content of 50% minimum. Paired-end libraries from fresh frozen tumour samples were prepared using the Agilent SureSelectXT HumanV5 kit for whole-genome sequencing (WGS). These were sequenced together with a tumour complementary DNA on an Illumina HiSeq2500 (paired-end 100 bp). Sequencing reads were mapped to the GRCh37 human reference genome using HISAT2

Dataset EGAD00001006540

ATAC data for Glioblastoma (EGAS00001003953, H016)

ATAC-seq data for 2 glioblastoma cell lines (LN229, ZH487), NT and SOX10KD.

Dataset EGAD00001006544

WGS data for Glioblastoma (EGAS00001003953, H016)

Whole genome sequencing data for 20 human glioblastoma patients.

Dataset EGAD00001006545

WGBS data for Glioblastoma (EGAS00001003953, H016)

Whole Genome Bisulfite data for human glioblastoma patients, EGAS00001003953. 68 human samples

Dataset EGAD00001006546

RNA data for Glioblastoma (EGAS00001003953, H016)

RNA data for human glioblastoma patients, EGAS00001003953. 64 human samples, 2 cell lines (LN229, ZH487).

Dataset EGAD00001006547

ChIPseq data for Glioblastoma (EGAS00001003953, H016)

ChIPseq data for human glioblastoma patients, EGAS00001003953. Mix of input, H3K27ac, H3K27me1, H3K27me3, H3K36me3, H3K4me1, H3K4me3, H3K9me3 and BRD, 20 human samples, 2 cell lines (LN229, ZH487).

Dataset EGAD00001006548

RNAseq of neuroblastoma PDX and cell lines

This dataset contains 72 RNAseq (BAM and Fastq files are available for each sample).

Dataset EGAD00001006558

ChIPseq of neuroblastoma

This dataset contains 4 samples (2x input and 2x H3K27ac ChIPseq) in the IC-pPDXC-63 cell line.

Dataset EGAD00001006557

scRNAseq of neuroblastoma patients

This dataset contains 19 scRNAseq realized on neuroblastoma patients biopsies straight after surgical act.

Dataset EGAD00001006556

FFPE

The mutational status of 112 recurrently mutated genes in B-cell lymphoma was examined by targeted next-generation sequencing (NGS). Libraries were performed with 150 ng of genomic DNA (gDNA) obtained from formalin-fixed paraffin-embedded (FFPE) biopsy using molecular-barcoded library adapters (ThruPLEX Tag-seq kit; Takara) coupled with a custom hybridization capture based method (SureSelect XT Target Enrichment System Capture strategy, Agilent Technologies Inc.) and sequenced in a MiSeq instrument (Illumina, 2x150bp).

Dataset EGAD00001006565

cfDNA

The mutational status of 112 recurrently mutated genes in B-cell lymphoma was examined by targeted next-generation sequencing (NGS). Libraries were performed with 15-30 ng of cfDNA obtained from plasma using molecular-barcoded library adapters (ThruPLEX Tag-seq kit; Takara) coupled with a custom hybridization capture based method (SureSelect XT Target Enrichment System Capture strategy, Agilent Technologies Inc.) and sequenced in a MiSeq instrument (Illumina, 2x150bp).

Dataset EGAD00001006566

CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase

Here we report successful gene knock-in (KI) in the eggs of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We targeted the acetylcholinesterase (AChE) gene of S. mansoni using two synthetic guide RNAs (gRNAs), X5 and X7, respectively. Liver eggs of S. mansoni were exposed to CRISPR-vector containing X5 or X7 by electroporation. Simultaneously, eggs were transfected with a ssODN donor encoding a stop codon in all six frames. Next generation sequencing analysis revealed that CRISPR/Cas9-mediated editing in S. mansoni eggs resulted in Homology-Directed Repair (HDR) when template DNA ssODN provided. Furthermore, soluble egg antigen (SEA) from AChE-modified eggs exhibited markedly reduced AChE activity compared with controls, indicative that programmed Cas9 cleavage mutated the AChE gene. Following injection of modified schistosome eggs into the tail veins of mice, a significant decrease in granuloma size in the lungs of these animals. Notably, an enhanced Th2 response induced by eggs in lung, and splenocytes small intestine-draining mesenteric lymph node cells was also generated in mice injected with X5-KI eggs in different methods. These findings further demonstrate the power and utility of CRISPR/Cas9-based genome editing for undertaking functional genomics studies in schistosomes.

Dataset EGAD00001006573

Systemic analysis of cutaneous and uveal melanoma liver metastases

RNAseq and WES of liver metastases samples (resections and biopsies) of CM and UM patients

Dataset EGAD00001006577

Neuroblastoma Cell Line Circle-seq Data

This dataset comprises Circle-seq data for 12 neuroblastoma cell lines supporting Koche et al. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma (2020).

Dataset EGAD00001006579

Primary Neuroblastoma Circle-seq Data

Circle-seq data for 21 primary neuroblastoma samples supporting Koche et al. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma (2020).

Dataset EGAD00001006580

Small molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma (methylation dataset)

human medulloblastoma xenograft isolated from mouse brain was frozen and genomic DNA or RNA was extracted. Bisulfite converted DNA was processed and hybridised to illumina EPIC or 450K arrays using standard protocols. RNAseq was performed on total RNA.

Dataset EGAD00001006583

RNA data of neuroblastoma patients

94 sample with multi-omics analysis of ALT-positive neuroblastoma tumors, rna sequencing

Dataset EGAD00001006587

RRBS analysis to characterize the epigenomic conservation between species in the context of Aging and Cancer.

This dataset contains Raw Reduced Representation DNA bisulfite-sequencing data obtained from human brain samples corresponding to 3 Young and 3 Old individuals (aging context), and 3 normal and 3 Glioblastoma samples (tumor context). RRBS libraries were prepared at Diagenode SA and samples were sequenced using the Illumina Novaseq6000 sequencing platform.The accompanying samples from this study (mouse tissues) are located at the ENA database under the accession number PRJEB41460.

Dataset EGAD00001006650

DKFZ-St.Jude Medulloblastoma - 41 MB germline cases, exome data

Germline exome tumor/control pairs for 41 medulloblastoma cases, MBG cohort sequenced on Illumina machines from the paper "Germline Elongator mutations in Sonic Hedgehog medulloblastoma" (Waszak et al. 2020 Nature).

Dataset EGAD00001006658

DKFZ-St.Jude Medulloblastoma - 218 CEF control exomes

218 control exomes, CEF cohort, sequenced on Illumina machines from the paper "Germline Elongator mutations in Sonic Hedgehog medulloblastoma" (Waszak et al. 2020 Nature).

Dataset EGAD00001006659

DKFZ-St.Jude Medulloblastoma - 8 MB cases, exome/WGS data

Tumor/Control pairs for 8 medulloblastoma cases, MB cohort, mixed exome and whole genome data, sequenced on Illumina machines from the paper "Germline Elongator mutations in Sonic Hedgehog medulloblastoma" (Waszak et al. 2020 Nature).

Dataset EGAD00001006660

DKFZ-St.Jude Medulloblastoma - 70 PAN-GATC control exomes

Exome controls for 70 individuals, PAN-GATC cohort, sequenced on Illumina machines from the paper "Germline Elongator mutations in Sonic Hedgehog medulloblastoma" (Waszak et al. 2020 Nature).

Dataset EGAD00001006661

DKFZ-St.Jude Medulloblastoma - 3 XI046 SF controls, WGS data

3 control whole genomes, SF cohort, sequenced on Illumina machines from the paper "Germline Elongator mutations in Sonic Hedgehog medulloblastoma" (Waszak et al. 2020 Nature).

Dataset EGAD00001006662

DKFZ-St.Jude Medulloblastoma - 9 SJMB tumor/control pairs, exome

9 tumor/control exomes, SJMB samples, sequenced on Illumina machines from the paper "Germline Elongator mutations in Sonic Hedgehog medulloblastoma" (Waszak et al. 2020 Nature).

Dataset EGAD00001006663

DKFZ-St.Jude Medulloblastoma - 6 TB control exomes

6 control exomes, TB cohort, sequenced on Illumina machines from the paper "Germline Elongator mutations in Sonic Hedgehog medulloblastoma" (Waszak et al. 2020 Nature).

Dataset EGAD00001006664

DKFZ-St.Jude Medulloblastoma - 225 clinical cases, control exomes with some paired tumor.

225 clinical cases, control exomes with some paired tumor data, sequenced on Illumina machines from the paper "Germline Elongator mutations in Sonic Hedgehog medulloblastoma" (Waszak et al. 2020 Nature).

Dataset EGAD00001006665

Mutational signatures in esophageal squamous cell carcinoma from eight countries of varying incidence – patient metatdata (Mutographs)

Dataset EGAD00001006732

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