Hypermethylation of antisense long noncoding RNAs in acute lymphoblastic leukemia.

Aim: Long noncoding RNAs serve critical regulatory functions highly specific for a tissue and its developmental stage. Antisense long ncRNA (AS-lncRNA) methylation changes in acute lymphoblastic leukemia (ALL) versus normal pre-B-cell lymphoblasts were evaluated to identify potential differential methylation in this group of genes.

Materials & Methods: The methylome of ALL and normal lymphoblasts was examined by the methylated CpG island recovery assay followed by NGS.

Risk of Osteosarcoma in Dogs After Open Fracture Fixation.

Objective: To critically evaluate whether open fracture fixation is a significant risk factor for latent osteosarcoma development.

Study Design: Case-control study.

Sample Population: Dogs undergoing open fracture repair and dogs diagnosed with osteosarcoma.

Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children under the age of 15. In addition to genetic aberrations, epigenetic modifications such as DNA methylation are altered in cancer and impact gene expression. To identify epigenetic alterations in ALL, genome-wide methylation profiles were generated using the methylated CpG island recovery assay followed by next-generation sequencing.

The expression of RUNDC3B is associated with promoter methylation in lymphoid malignancies.

DNA methylation is an epigenetic modification that plays an important role in the regulation of gene expression. The function of RUNDC3B has yet to be determined, although its dysregulated expression has been associated with malignant potential of both breast and lung carcinoma. To elucidate the potential of using DNA methylation in RUNDC3B as a biomarker in lymphoid malignancies, the methylation status of six regions spanning the CpG island in the promoter region of RUNDC3B was determined in cancer cell lines.

Genome-wide DNA methylation analysis in precursor B-cells.

DNA methylation is responsible for regulating gene expression and cellular differentiation and for maintaining genomic stability during normal human development. Furthermore, it plays a significant role in the regulation of hematopoiesis. In order to elucidate the influence of DNA methylation during B-cell development, genome-wide DNA methylation status of pro-B, pre-BI, pre-BII, and naïve-B-cells isolated from human umbilical cord blood was determined using the methylated CpG island recovery assay followed by next generation sequencing.

Uncovering influence links in molecular knowledge networks to streamline personalized medicine.

Objectives: We developed Resource Description Framework (RDF)-induced InfluGrams (RIIG) - an informatics formalism to uncover complex relationships among biomarker proteins and biological pathways using the biomedical knowledge bases. We demonstrate an application of RIIG in morphoproteomics, a theranostic technique aimed at comprehensive analysis of protein circuitries to design effective therapeutic strategies in personalized medicine setting.

Methods: RIIG uses an RDF "mashup" knowledge base that integrates publicly available pathway and protein data with ontologies.

Automated extraction of precise protein expression patterns in lymphoma by text mining abstracts of immunohistochemical studies.

Background: In general, surgical pathology reviews report protein expression by tumors in a semi-quantitative manner, that is, -, -/+, +/-, +. At the same time, the experimental pathology literature provides multiple examples of precise expression levels determined by immunohistochemical (IHC) tissue examination of populations of tumors. Natural language processing (NLP) techniques enable the automated extraction of such information through text mining.

Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia.

We conducted a genome-wide DNA methylation analysis in CD19 (+) B-cells from chronic lymphocytic leukemia (CLL) patients and normal control samples using reduced representation bisulfite sequencing (RRBS). The methylation status of 1.8-2.

A pathologist-in-the-loop IHC antibody test selection using the entropy-based probabilistic method.

Background: Immunohistochemistry (IHC) is an important tool to identify and quantify expression of certain proteins (antigens) to gain insights into the molecular processes in a diseased tissue. However, it is a challenge for pathologists to remember the discriminative characteristics of the growing number of such antigens across multiple diseases. The complexity of their expression patterns, fueled by continuous discoveries in molecular pathology, gives rise to a combinatorial explosion that places an unprecedented burden on a practicing pathologist and therefore increases cost and variability of IHC studies.

Large-scale analysis of DNA methylation in chronic lymphocytic leukemia.

Aims: B-cell chronic lymphocytic leukemia (CLL) is a heterogeneous malignancy that clinically ranges from indolent to rapidly progressive. CLL, like other cancers, can be affected by epigenetic alterations.

Materials & Methods: A microarray discovery-based study was initiated to determine DNA methylation in CLL cases with a range of CD38 expression (1–92%).

Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia.

Certain WNT and WNT network target genes are expressed at higher or lower levels in chronic lymphocytic leukemia compared with normal B-cells. This includes upregulation of nuclear complex genes, as well as genes for cytoplasmic proteins and WNT ligands and their cognate receptors. In addition, epigenetic silencing of several negative regulators of the WNT pathway have been identified.

Hypermethylation of the DLC1 CpG island does not alter gene expression in canine lymphoma.

Background: This study is a comparative epigenetic evaluation of the methylation status of the DLC1 tumor suppressor gene in naturally-occurring canine lymphoma. Canine non-Hodgkin's lymphoma (NHL) has been proposed to be a relevant preclinical model that occurs spontaneously and may share causative factors with human NHL due to a shared home environment. The canine DLC1 mRNA sequence was derived from normal tissue.

DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma.

High-throughput microarray technologies were used to study DNA methylation accompanied by transcriptional changes in follicular lymphoma (FL). Using Methylated CpG Island Amplification with Microarrays to study CpG Island DNA methylation in FL, we discovered widespread hypermethylation of homeobox genes and previously identified targets of polycomb repressive complex 2 (PRC2) in cell lines and primary tumors, but not in benign follicular hyperplasia (BFH). DNA methylation for HOXA11, HOXD10, HOXB7, HOXC12, PAX6, LHX9, SFMBT2, EN2, and PAX7 was independently validated in the RL cell line and HOXA11, HOXD10, PAX6, and EN2 in primary tumors.

Mapping biomedical literature with WNT signaling pathway.

Epigenetic studies in cancer pathways have been essential in helping scientists understand the key players in cancer. Gene relationships reported in biomedical literature are valuable to understand the interaction network. Nevertheless, biomedical literature is growing rapidly and the scientific community needs a mechanism to have up-to-date pathways that reflect the new findings from the literature.

Relational analysis of CpG islands methylation and gene expression in human lymphomas using possibilistic C-means clustering and modified cluster fuzzy density.

Heterogeneous genetic and epigenetic alterations are commonly found in human non-Hodgkin's lymphomas (NHL). One such epigenetic alteration is aberrant methylation of gene promoter-related CpG islands, where hypermethylation frequently results in transcriptional inactivation of target genes, while a decrease or loss of promoter methylation (hypomethylation) is frequently associated with transcriptional activation. Discovering genes with these relationships in NHL or other types of cancers could lead to a better understanding of the pathobiology of these diseases.

Large-scale CpG methylation analysis identifies novel candidate genes and reveals methylation hotspots in acute lymphoblastic leukemia.

This study examined DNA methylation associated with acute lymphoblastic leukemia (ALL) and showed that selected molecular targets can be pharmacologically modulated to reverse gene silencing. A CpG island (CGI) microarray containing more than 3,400 unique clones that span all human chromosomes was used for large-scale discovery experiments and led to 262 unique CGI loci being statistically identified as methylated in ALL lymphoblasts. The methylation status of 10 clones encompassing 11 genes (DCC, DLC-1, DDX51, KCNK2, LRP1B, NKX6-1, NOPE, PCDHGA12, RPIB9, ABCB1, and SLC2A14) identified as differentially methylated between ALL patients and controls was independently verified.

OntoQuest: a physician decision support system based on ontological queries of the hospital database.

OntoQuest is a physician decision support system that mines the hospital data base for previous decisions made in cases similar to the current one. For example, OntoQuest displays a list of the medications prescribed to similar historical patients from which the physician may compare his choice of medication for the current patient. This information retrieval is accomplished using ontological queries.