Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Cancer diagnoses profile of bone marrow specimens from November 2012 to December 2015 in a tertiary academic setting

This study aimed to examine the number and type of cancer diagnoses made based on bone marrow aspirates (BMA) using morphology and/or histology, over a three year period. All the data collected (2012-2015) was obtained using the Trak-Care laboratory information system (LIS) of the National Health Laboratory Service (NHLS). Data was categorised into four categories including acute leukaemias (ALs), chronic leukaemias (CLs), Hodgkin’s lymphoma (HL), Non-Hodgkin’s lymphoma (NHL) and a miscellaneous group. The laboratory test most frequently used to make diagnoses was bone marrow aspiration (BMA) morphology (199), followed by flow cytometry (138), histology (113), fluorescent in situ hybridisation (FISH) (54) and polymerase chain reaction (PCR) (9). In total, the top three conditions diagnosed were acute myeloid leukaemias (AMLs), chronic myeloid leukaemia (CML) and B-cell acute lymphoblastic leukaemia (B-ALL). There was good agreement between the diagnoses made by BMA morphology, BMT histology and flow cytometry. Results showed that BMA morphology was the most popular diagnostic test used and that this test had excellent agreement with BMT histology and flow cytometry diagnoses. The most frequently diagnosed conditions were the AMLs.http://www.smltsa.org.za/publications.htmlam2018Haematolog

Retrospective data analysis of all requests for flow cytometric immunophenotyping in a tertiary hospital setting

Flow cytometry is a globally accepted diagnostic tool used for the rapid identification of cells based on their surface and intracellular antigens, especially for the diagnosis of haematological malignancies. The aim of this study was to evaluate the requests received for flow cytometric immunophenotyping and to create a profile of diagnoses. In 2014 data regarding indications and diagnoses were captured from request forms received and final diagnosis reports issued by the Tshwane Academic Division (TAD) of the National Health Laboratory Service (NHLS). A total of 1234 requests were received over the one year period, of which 80.4% were performed and 16.8 % were rejected. The most common indications were leukaemia, lymphoma and cytopenia. Nineteen percent of requests received contained no correct indication or clinical history. In total, 103 and 153 diagnoses were established based on peripheral blood and bone marrow aspirate specimens respectively. Samples were mostly rejected due to sample clotting, electronic gate keeping rules and receiving the specimen more than 24 hours after collection.http://www.smltsa.org.za/publications.htmlam2018Haematolog

The correlation between C-reactive protein and toxic granulation of neutrophils in the peripheral blood

BACKGROUND: During inflammation, the serum concentrations of granulocyte colony-stimulating factor (G-CSF), plasma interleukin-6 (IL-6), and C-reactive protein (CRP) increase. A positive correlation between CRP and the percentages of neutrophils exhibiting toxic granulation during inflammation has been demonstrated, and that the fluctuations of CRP and toxic granulation of neutrophils were similar. OBJECTIVES: We studied whether grading of toxic granulated neutrophils can be used as a surrogate marker for infection or inflammation, and also be an easier method than previously described methods. MATERIALS AND METHODS: We graded 357 consecutive peripheral blood slides from patients on whom a full blood count with differential count and CRP level was performed, according to intensity of toxic granulation in the neutrophil population, according to a newly proposed grading system. RESULTS: The CRP range was between 1 and 530.3 mg/l. The results confirm the association between a rise in CRP and progressive intensity of toxic granulation in neutrophils in peripheral blood. Kruskal-Wallis equality of populations rank test showed a statistically significant difference between the graded categories (p=0.0001). The Trend test was also statistically significant (p=0.000). CONCLUSION: The proposed system can be applied to patients with inflammatory or infectious conditions, where grading of toxic granulation of neutrophils can possibly be used as a surrogate marker to assess infection or inflammation and their response to treatment. It may be of particular use in cases where traditional infectious or inflammatory markers cannot be used, owing to inherent problems associated with the respective conditions

The impact of collection tube fill volume on international normalized ratio

INTRODUCTION: Pre-analytical variability currently represents the most important source of errors that can lead to inaccurate patient results in monitoring of patients being treated with oral anticoagulant therapy. The volume of blood collected is critical for accurate coagulation results. The National Committee for Clinical Laboratory Standards (NCCLS) recommends a ratio of blood to anticoagulant volume of 9:1. However, investigators have published reports which suggest that a lower ratio may be acceptable. Unfortunately the recommendations of these reports are inconsistent. AIM: The aim of this study was to determine the impact of tube fill volume on INR values both in healthy subjects and patients receiving oral anticoagulation therapy. METHODS: INR values were obtained by processing coagulation specimens containing different volumes of whole blood. The study group included 30 patients taking oral anticoagulation therapy and 15 healthy volunteers. Respectively 2.5ml, 3 ml, 3.5 ml, 4 ml and 4.5 ml of whole blood was drawn into tubes containing a fixed volume of 3.2% (0.109M) sodium citrate. RESULTS: The INR values increased as total tube fill volumes decreased for both groups but this finding did not reach statistical significance in either group for the tube fill volumes studied. CONCLUSION: For blood specimens collected in 3.2% citrate anticoagulant, a total tube fill volume of greater than 56% yielded reliable INR resultshttp://www.smltsa.org.z