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• Patient-derived tumoroids from CIC::DUX4 rearranged sarcoma identify MCL1 as a therapeutic target

  High-risk sarcomas, such as metastasized and relapsed Ewing and CIC-rearranged sarcomas, currently lack effective curative systemic treatment options. Precision medicine approaches offer hope and among them ex vivo drug response profiling of patient-derived tumor cells emerges as a promising novel tool to identify effective drugs for individual patients. Here, we established ex vivo culture conditions to propagate Ewing and CIC::DUX4-sarcomas as tumoroids in a co-clinical manner. These models retained their original molecular and functional characteristics, including recurrent ARID1A mutations, and serve as tumor avatars suitable for large-scale drug testing. Indeed, screening a large drug library on a small living biobank of such tumors not only revealed distinct response differences between the two entities, but also identified an exceptional dependency of CIC::DUX4-sarcoma cells on MCL1. Mechanistically. MCL1 was identified as a direct target gene of the CIC::DUX4 fusion protein. Genetic and pharmacological inhibition of MCL1 induced rapid apoptosis in CIC::DUX4-sarcoma cells and inhibited tumor growth in a xenograft model. Thus, MCL1 represents a potential novel therapeutic target for CIC::DUX4-sarcoma. Overall, our study highlights the feasibility of co-clinical drug response profiling for individual sarcoma cases and suggests that prospective tests, to evaluate its clinical benefit are highly warranted.

  Study EGAS00001008039

• ATAC-seq of a selected group of AML cases

  ATAC-seq data were generated for a number of selected patients to investigate changes in enhancer and promoter regions. ATAC-seq was essentially carried out as described in31. Briefly, prior to transposition the viability of the cells was assessed and 1 × 106 cells were treated in culture medium with DNase I (Sigma) at a final concentration of 200 U ml−1 for 30 minutes at 37 °C. After Dnase I treatment, cells were washed twice with ice-cold PBS, and cell viability and the corresponding cell count were assessed. 5 × 104 cells were aliquoted into a new tube and spun down at 500 × g for 5 minutes at 4 °C, before the supernatant was discarded completely. The cell pellet was resuspended in 50 µl of ATAC-RSB buffer (10 mM Tris-HCl pH 7.4, 10 mM NaCl, 3 mM MgCl2) containing 0.1% NP-40, 0.1% Tween-20, and 1% Digitonin (Promega), and was incubated on ice for 3 minutes to lyse the cells. Lysis was washed out with 1 ml of ATAC-RSB buffer containing 0.1% Tween-20. Nuclei were pelleted at 500 × g for 10 minutes at 4 °C. The supernatant was discarded carefully and the cell pellet was resuspended in 50 µl of transposition mixture (25 µl 2× tagment DNA buffer, 2.5 µl transposase (100 nM final; Illumina), 16.5 µl PBS, 0.5 µl 1% digitonin, 0.5 µl 10% Tween-20, 5 µl H2O) by pipetting up and down six times. The reaction was incubated at 37 °C for 30 minutes with mixing before the DNA was purified using the Monarch PCR & DNA Cleanup Kit (NEB) according to the manufacturer’s instructions. Purified DNA was eluted in 20 µl elution buffer (EB) and 10 µl purified sample was objected to a ten-cycle PCR amplification using Nextera i7- and i5-index primers (Illumina). Purification and size selection of the amplified DNA were carried out with Agencourt AMPure XP beads. For purification the ratio of sample to beads was set to 1:1.8, whereas for size selection the ratio was set to 1:0.55. Purified samples were eluted in 15 µl of EB. Quality and concentration of the generated ATAC libraries were analyzed using the High Sensitivity D1000 ScreenTape Kit (Agilent) and libraries were sequenced paired-end on a NovaSeq (Illumina). ATAC-seq reads were aligned to the human reference genome build hg19 with bowtie2

  Dataset EGAD00001007583

• Exome Chip Study of NIMH Controls

  Here, we report exome chip genotyping results of 1052 samples from the NIMH control set, a collection of healthy controls for general research use. The samples are all unrelated.

  Study phs000630

• 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

• RGB TGCT Data Access Committee

  The RGB TGCT Data Access Committee is responsible for reviewing and approving requests for access to controlled genomic data generated from testicular germ cell tumor (TGCT) patients treated at the National Cancer Institute of Mexico (INCan). The committee evaluates requests to ensure that data use complies with the informed consent provided by participants and with applicable institutional and ethical regulations.

  Dac EGAC50000000959

• Genomewide Association Study of Inflammatory Bowel Disease

  WTCCC genome-wide case-control association study for Inflammatory Bowel Disease (IBD) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.

  Study EGAS00000000006

• Saliva Microbiota of Finnish children from the PANIC study

  Saliva Microbiota of Finnish children aged between 6-8 yrs in the PANIC study. Baseline data. Studied for various lifestyle conditions and oral diseases (without caries/with caries).

  Study EGAS50000000708

• RNA-sequencing of ex situ stimulated donors blood cells

  Cells from whole blood stimulation assay were cryopreserved. The cryopreserved cells were thawed and subjected to RNA preparation. RNA obtained were subjected to for bulk sequencing.

  Study EGAS50000001077

• Tumor heterogeneity and immune-evasive microenvironment in T follicular helper cell lymphomas

  Single-cell analysis data for tumor and immune cells from lymph node and peripheral blood samples of 14 patients with T follicular helper cell lymphomas

  Study EGAS50000000275

• Liquid biopsy-based minimal residual disease monitoring for early risk stratification and decision-making in advanced non-small cell lung cancer - Biobank co-hort

  Liquid biopsies generated for minimal residual disease monitoring of advanced non-small cell lung cancer. Ultra deep targeted sequencing of lung cancer specific genes, with UMIs. This dataset consists of the biobank cohort

  Dataset EGAD50000002231