Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

Visualization Techniques of Time-Oriented Data for the Comparison of Single Patients With Multiple Patients or Cohorts: Scoping Review

BackgroundVisual analysis and data delivery in the form of visualizations are of great importance in health care, as such forms of presentation can reduce errors and improve care and can also help provide new insights into long-term disease progression. Information visualization and visual analytics also address the complexity of long-term, time-oriented patient data by reducing inherent complexity and facilitating a focus on underlying and hidden patterns. ObjectiveThis review aims to provide an overview of visualization techniques for time-oriented data in health care, supporting the comparison of patients. We systematically collected literature and report on the visualization techniques supporting the comparison of time-based data sets of single patients with those of multiple patients or their cohorts and summarized the use of these techniques. MethodsThis scoping review used the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist. After all collected articles were screened by 16 reviewers according to the criteria, 6 reviewers extracted the set of variables under investigation. The characteristics of these variables were based on existing taxonomies or identified through open coding. ResultsOf the 249 screened articles, we identified 22 (8.8%) that fit all criteria and reviewed them in depth. We collected and synthesized findings from these articles for medical aspects such as medical context, medical objective, and medical data type, as well as for the core investigated aspects of visualization techniques, interaction techniques, and supported tasks. The extracted articles were published between 2003 and 2019 and were mostly situated in clinical research. These systems used a wide range of visualization techniques, most frequently showing changes over time. Timelines and temporal line charts occurred 8 times each, followed by histograms with 7 occurrences and scatterplots with 5 occurrences. We report on the findings quantitatively through visual summarization, as well as qualitatively. ConclusionsThe articles under review in general mitigated complexity through visualization and supported diverse medical objectives. We identified 3 distinct patient entities: single patients, multiple patients, and cohorts. Cohorts were typically visualized in condensed form, either through prior data aggregation or through visual summarization, whereas visualization of individual patients often contained finer details. All the systems provided mechanisms for viewing and comparing patient data. However, explicitly comparing a single patient with multiple patients or a cohort was supported only by a few systems. These systems mainly use basic visualization techniques, with some using novel visualizations tailored to a specific task. Overall, we found the visual comparison of measurements between single and multiple patients or cohorts to be underdeveloped, and we argue for further research in a systematic review, as well as the usefulness of a design space