BackgroundThe oncogenic potential of Epstein-Barr virus (EBV) in breast cancer is being increasingly recognized. Despite some controversies regarding such role, new evidence is suggesting a culpability of EBV in breast cancer, particularly in Africa where the virus has been originally associated with causation of several solid and hematological malignancies. One example is a report from Sudan implicating EBV as a prime etiologic agent for an aggressive type of breast cancer, where nearly 100% of tumor tissues were shown to carry viral signatures. To get a broader view on such association, other nearby countries should be investigated. The present study aims to determine the prevalence and possible associations of the virus in Eritrean breast cancer patients.MethodsDetection of EBV genome using primers that target Epstein Barr Encoded RNA (EBER) gene and Latent Membrane Protein-1 (LMP-1) gene sequences was performed by polymerase chain reaction (PCR) on DNA samples extracted from 144 formalin fixed paraffin embedded breast cancer tissues and 63 non-cancerous breast tissue as control group. A subset of PCR positive samples was evaluated for EBER gene expression by in situ hybridization (ISH). Expression of Latent Membrane Protein-2a (LMP2a) was also assessed by immunohistochemistry in a subset of 45 samples.ResultsBased on PCR results, EBV genome signals were detected in a total of 40 samples (27.77%) as compared to controls (p-value = 0. 0031) with a higher sensitivity when using the EBER primers. Five out of the 14 samples stained by EBER-ISH 35.71% were positive for the virus indicating the presence of the viral genome within the tumor cells. Of those stained for IHC 7 (15.55%) were positive for LMP2a showing low viral protein frequency.ConclusionsBased on these findings it can be concluded that EBV in Eritrea is associated with a smaller subset of tumors, unlike neighboring Sudan, thus pointing to possible differences in population predisposition and diseases epidemiology.

Background: Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a pilot genome-wide methylome study to characterize aberrant DNA methylation in breast cancer.Results: Differential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20,188 differentially methylated positions (DMPs), which is further divided into 13,633 hypermethylated sites corresponding to 5339 genes and 6,555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC.Conclusion: Our results clearly show the utility of epigenetic assays in interrogating breast cancer tumorigenesis, and pinpointing specific developmental and viral pathways dysregulation that might serve as potential biomarkers or targets for therapeutic interventions.

We coincubated killed or live human immunodeficiency virus type-1 (HIV-1) with human monocyte-derived cells infected with Leishmania donovani and examined the effect of the virus preparations on the intracellular growth of the parasite. We found that there was significant enhancement (by a mean of 53%, p < 0.001) of intracellular L. donovani growth in the human monocytic leukaemia THP-1 cell line coincubated with killed HIV-1. Infection of peripheral blood monocyte-derived macrophages with live HIV-1 initiated after L. donovani infection led to an increase in intracellular parasites by an overall mean of 2.8% vs 4.9% (p < 0.01) at 2 and 5 d after HIV infection in L. donovani and L. donovani plus HIV-1 infected, respectively, and by an overall mean of 5.0% vs 13.3% (p < 0.001) at 5, 12 and 15 d after HIV-1 infection in L. donovani and L. donovani + HIV-1 infected, respectively. Further, L. donovani infection 2 d after infection with HIV-1 led to enhanced parasite growth (34.5%, p < 0.001) compared with cells infected with L. donovani alone (5.5%), and those where HIV-1 was added after L. donovani (18.1%). In all cases, HIV-1 from live and killed virus preparations led to decreased anti-leishmanial activity of the macrophages as evidenced by decreased control of intracellular multiplication. The findings may suggest a mechanism not requiring live virus to explain how HIV-1 coinfection may impair the control of intracellular Leishmania growth in individuals with pre-existing asymptomatic infection leading to the reactivation of the parasite. Moreover, patients with HIV-1 infection might be at increased risk of developing Leishmania infection.

The Epstein Barr Virus is among the very first oncogenic viruses to be identified as culprits of human malignancies. Its role as an etiologic agent of breast cancer however remains debated despite mounting molecular evidence. In this chapter we address the challenge of multiple molecular etiologies of breast cancer (BC) with emphasis on the Epstein Barr Virus (EBV) as a potential causative agent within a frame work of gene/environment interaction. We also hope to contribute to a critique of the a concept of universal single agent or gene in cancer etiology. In addition to reviewing further reasons of why EBV should be considered a tumor virus, coupling molecular targets at the initiation stage, we examine evidence for the culpability of EBV as oncogenic virus in relation to the genetic and epigenetic events that leads to carcinogenesis of cancer; and the subsequent downstream interaction including genetic and epigenetic modifiers of signaling and molecular function underlying the cancerous phenotype. The TNF family is taken as an example of how the epigenetic reprogramming process, impacts molecular targets and how these combined interplay of molecular events impinges on pathogenesis and malignancy of breast cancer in humans.

BackgroundBreast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a genome-wide methylome study to characterize aberrant DNA methylation in breast cancer. ResultsDifferential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20188 differentially methylated positions (DMPs), which is further divided into 13633 hypermethylated sites corresponding to 5339 genes and 6555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC ConclusionOur results clearly show the utility of epigenetic assays in interrogating breast cancer tumorigenesis, and pinpointing specific developmental and viral pathways dysregulation that might serve as potential biomarkers or targets for therapeutic interventions. KeywordsMethylome, Breast Cancer, Epigenetics, DNA Methylation, HM450, Epigenome Reference. BackgroundBreast cancer (BC) is the most common cancer among females in Sudan [1][2][3], and is still a leading cause of high morbidity and mortality across the world. According to a recent report from the national cancer registry[2], BC had an incidence rate of 25.1 per 100.000, more than twice the incidence rate of the second commonest cancer.Furthermore, Sudanese BC patients tend to present at young age, at late stage, and with advanced disease compared to their counterparts in other countries [4]. Another study [5] reported a young age of presentation for locally advanced BC. Therefore, there is an urgent need for serious epidemiologic and molecular studies in order to trace the underlying mechanisms behind BC, and for developing better early detection methods as well as a nationwide educational effort to tackle this ravaging disease.Epigenetics has emerged as a new, rapidly growing field in biology, with significant implications for cancer research. Epigenetic modifications include DNA methylation, and histone modifications, although they both do not alter DNA sequence per se, they influence chromatin remodeling and thus offer a dynamic and flexible way of controlling gene expression.DNA methylation of cytosine residues occurs predominantly at CpG sites, and is mediated by three DNA methyltransferases (DNMTs). DNMT1, which maintains DNA methylation during cell replication, and a pair of DNMT3s -DNMT3a and DNMT3bwhich is responsible for de novo DNA methylation. Epigenetic reprogramming through genome-wide alteration of DNA methylation (methylome) is critical for control of development and differentiation in normal cells and tissues, however, faulty epigenetic reprogramming, as in aberrant DNA methylation...

Purpose: Olfactory receptors are G protein coupled surface receptors (GPCRs) of which their ectopic expression is currently of mounting interest to the development and metastasis of malignancies. These genes having a direct contact with the environment may probably be stimulated by various factors which can bring about methylation aberrations, including DNA hypo and hyper-methylation. Here we gather clues from epigenetic and phenotypic data in order to further our understanding of the potential association of the olfaction with oncogenesis.Methods: Whole methylome dataset of breast cancer series generated by Illumina Infinium Human Methylation 450 Bead Chip was interrogated for differentially methylated genes and further subject to network analysis using various search tools. Analysis of putative phenotypic trait in olfaction function was performed using smell detection and smell identification tests and data was analyzed using Mann-Whitney test.Results: Sixty-eight differentially methylated ORs were enriched mainly on chromosomes 1q23, and 11p15, specifically 1q44 (P value 6.867e-20). Amongst the disease signatures of these hypomethylation events was breast cancer itself (P value 0.004437). Network analysis suggests the interaction of differentially hypo and hyper methylated olfactory receptor genes might be pivotal in stimulating several important biological pathways including circadian genes and pathways potentially associated with metastasis. Phenotypic smell test shows a generalized impairment of smell capability in breast cancer patients as compared to controls (Mann-Whitney Test P=0.0001), an effect that is independent of chemotherapyConclusions: The olfaction appears as a crucial element in carcinogenesis, evident by both phenotypic and genotypic (epigenetic) data in a well characterized breast cancer subset.