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• Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia

  In BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1, is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness, and poor patient outcomes. A later arrest was associated with lineage fidelity, deep and durable leukemia remissions, and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1+ pre-leukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI-efficacy is an unexpected outcome of the differentiation stage at which this leukemia transforms.

  Study EGAS00001007167

• cfRRBS on cfDNA from pediatric cancer

  In the clinical management of pediatric solid tumors, histological examination of tumor tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumor is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner.

  Study EGAS00001004194

• An IL-1β driven neutrophil-stromal cell axis fosters a BAFF-rich microenvironment in multiple myeloma

  The bone marrow is continuously occupied by high numbers of neutrophils, and a tumor-supportive bias of these cells could significantly impact bone marrow-confined malignancies. In multiple myeloma, the bone marrow is characterized by inflammatory stromal cells with the potential to influence neutrophils. Here, we investigated myeloma-associated alterations in marrow neutrophils and the impact of stromal inflammation on neutrophil function. Mature neutrophils in myeloma marrow are activated and tumor-supportive, transcribing increased levels of pro-inflammatory cytokines, including IL-1β, and myeloma cell survival factors, such as the BCMA-ligand BAFF. Neutrophils were re-activated after first-line treatment, while this regimen reduced, but did not normalize, stromal inflammation. Interactions with inflammatory stroma induced neutrophil activation, including BAFF secretion, in a STAT3-dependent manner and once activated, neutrophils gained the ability to reciprocally induce stromal activation. Combined, our data define the presence of a neutrophil-stromal cell feed-forward loop driving tumor-supportive inflammation that could impact disease recurrence.

  Study EGAS00001007038

• Treatment of genetic screening of hypertriglyceridemia type I, III, and V - HTG Amsterdam

  This is a cohort of patients with extreme hypertriglyceridemia. Patients have been screened for loss of function mutations in LPL, GPIHBP1, APOC2, APOA5 and LMF1.

  Study phs000511

• cfRRBS data plasma healthy donors

  This is cfRRBS data produced from the cfDNA in plasma isolated from healthy, adult donors. Used as a reference for background signal in diseased (onclolytic) plasma cfDNA.

  Study EGAS50000000376

• Prognostic_factors_in_prostate_cancer__deep_sequencing_pilot_project_TAPG

  This is a pilot project to determine whether the TAPG FFPE DNA’s are suitable for deep sequencing. If successful an investigation of SNP distribution in a larger cohort will follow.

  Study EGAS00001000879

• Targeted long-read snIso-Seq of the human brain in neurodegenerative diseases

  Nuclei were extracted from postmortem human brain, and cDNA libraries were generated using the 10X Genomics 3' v3.1 kit. Prior to fragmentation, 75% of the library was reserved for long-read sequencing. This unfragmented library was used for target enrichment with a custom 50 gene probe panel from Twist Biosciences. The resulting amplified cDNA libraries were sequenced on a Sequel II. The files provided have undergone CCS generation, and we recommend following the guidelines in https://isoseq.how/ for further analysis starting with removal of primers using lima. The primer sequences that should be supplied are the Read 1 and TSO primers from the 10X Genomics kit.

  Dataset EGAD50000000179

• Immune Profiles Study

  This study assesses glioma patient blood methylation longitudinally beginning pre-surgery through other clinically important timepoints. Progression and survival are studied in relation to methylation derived immunologic profiles and other characteristics. For this study, patients scheduled for surgery at University of California San Francisco (UCSF) for a possible newly diagnosed glioma (grades 2-4) or recurrent grade 2/3 glioma were consented and enrolled. Patients had blood collected pre-surgery and, if the pathology results confirm a glioma, every few weeks or months during their treatment (up to 30 total timepoints). Blood immunomethylomic profiles were measured at these timepoints to assess associations with glioma patient outcomes, clinical measures, other known prognostic markers, and imaging characteristics.

  Study phs002998

• RNA Sequencing of paediatric patients with B lymphoblastic leukemia

  RNA sequencing was performed on 148 Bone marrow of peripheral blood samples of paediatric patients with B-ALL.

  Study EGAS00001004532

• Single-cell transcriptome of T-ALL PDX under drug treatment

  PDX model of T-ALL under treatment of CB-103 and Vehicle was analyzed by single-cell transcriptomics using 10X Genomics technology.

  Dataset EGAD00001009172