http://genomemedicine.com The latest research articles published by Genome Medicine 2012-01-31T00:00:00Z Inflammation represents the body's natural response to tissue damage; however, chronic inflammation may activate cell proliferation and induce deregulation of cell death in affected tissues. Chronic inflammation is an important factor in the development of hepatocellular carcinoma (HCC), although the precise underlying mechanism remains unknown. Epigenetic events, which are considered key mechanisms in the regulation of gene activity states, are also commonly deregulated in HCC. Here, we review the evidence that chronic inflammation might deregulate epigenetic processes, thus promoting oncogenic transformation, and we propose a working hypothesis that epigenetic deregulation is an underlying mechanism by which inflammation might promote HCC development. In this scenario, different components of the inflammatory response might directly and indirectly induce changes in epigenetic machineries ('epigenetic switch'), including those involved in setting and propagating normal patterns of DNA methylation, histone modifications and non-coding RNAs in hepatocytes. We discuss the possibility that self-reinforcing cross-talk between inflammation and epigenetic mechanisms might amplify inflammatory signals and maintain a chronic state of inflammation culminating in cancer development. The potential role of inflammation-epigenome interactions in the emergence and maintenance of cancer stem cells is also discussed. http://genomemedicine.com/content/4/1/8 Marion Martin Zdenko Herceg Genome Medicine 2012, null:8 2012-01-31T00:00:00Z doi:10.1186/gm307 From hepatitis to hepatocellular carcinoma Marion Martin and Zdenko Herceg discuss how cross-talk between inflammation and epigenetic mechanisms might be involved in the development of liver cancer. /content/figures/gm307-toc.gif Genome Medicine 1756-994X ${item.volume} 8 2012-01-31T00:00:00Z XML Epigenetic alterations, such as aberrant DNA methylation, are a hallmark of cancer. DNA hypermethylation of the promoter region affects, for example, the expression of tumor suppressor genes and is associated with their transcriptional silencing in tumors. A recent report has provided evidence for epigenetic silencing of the multispecific organic cation transporter SLC22A1 in hepatocellular carcinoma. Given the role of this transporter in the cellular uptake of several anticancer drugs, the study provided a novel mechanism to explain the substantial variability in treatment response, and it might provide a new strategy for optimization of pharmacotherapy of hepatocellular carcinoma.See research article http://www.genomemedicine.com/content/3/12/82 http://genomemedicine.com/content/4/1/10 Oliver Zolk Martin Fromm Genome Medicine 2012, null:10 2012-01-31T00:00:00Z doi:10.1186/gm309 Drug transporter regulation Oliver Zolk and Martin Fromm highlight a recent observation that uptake transporters for anticancer drugs are epigenetically regulated in hepatocellular carcinoma. /content/figures/gm309-toc.gif Genome Medicine 1756-994X ${item.volume} 10 2012-01-31T00:00:00Z XML Exome sequencing analysis is a cost-effective approach for identifying variants in coding regions. However, recognizing the relevant single nucleotide variants, small insertions and deletions remains a challenge for many researchers and diagnostic laboratories typically do not have access to the bioinformatic analysis pipelines necessary for clinical application. The Atlas2 suite, recently released by Baylor Genome Center, is designed to be widely accessible, runs on desktop computers but is scalable to computational clusters, and performs comparably with other popular variant callers. Atlas2 may be an accessible alternative for data processing when a rapid solution for variant calling is required.See research article http://www.biomedcentral.com/1471-2105/13/8. http://genomemedicine.com/content/4/1/7 Hanlee Ji Genome Medicine 2012, null:7 2012-01-30T00:00:00Z doi:10.1186/gm306 Improving bioinformatic pipelines Hanlee Ji discusses the Atlas2 suite, a new set of tools for calling variants in exome sequencing data that is faster and easier to use than comparable tools and could thus be useful in diagnostics. /content/figures/gm306-toc.gif Genome Medicine 1756-994X ${item.volume} 7 2012-01-30T00:00:00Z XML A report on the 6th International Conference on Genomics (ICG-VI), Shenzhen, China, 12-15 November 2011. http://genomemedicine.com/content/4/1/4 Jingde Zhu Genome Medicine 2012, null:4 2012-01-30T00:00:00Z doi:10.1186/gm303 Giant leaps in genome research? Jingde Zhu presents the recent progress made and highlights of the Beijing Genomics Institute's 6th International Conference on Genomics (ICG-VI), held in Shenzhen, China. /content/figures/gm303-toc.gif Genome Medicine 1756-994X ${item.volume} 4 2012-01-30T00:00:00Z XML {no abstract} http://genomemedicine.com/2012/4/1/9 Charles Auffray Timothy Caulfield Muin Khoury James Lupski Matthias Schwab Timothy Veenstra Genome Medicine 2012, null:9 2012-01-30T00:00:00Z doi:10.1186/gm308 Genomic medicine highlights of the year An editorial by our Section Editors provides their highlights of the past year and hints at likely future developments in genomic medicine. /content/figures/gm308-toc.gif Genome Medicine 1756-994X ${item.volume} 9 2012-01-30T00:00:00Z XML Most of the recently identified autoimmunity loci are shared among multiple autoimmune diseases. The pattern of genetic association with autoimmune phenotypes varies, suggesting that certain subgroups of autoimmune diseases are likely to share etiological similarities and underlying mechanisms of disease. In this review, we summarize the major findings from recent studies that have sought to refine genotype-phenotype associations in autoimmune disease by identifying both shared and distinct autoimmunity loci. More specifically, we focus on information from recent genome-wide association studies of rheumatoid arthritis, ankylosing spondylitis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes and inflammatory bowel disease. Additional work in this area is warranted given both the opportunity it provides to elucidate pathogenic mechanisms in autoimmunity and its potential to inform the development of improved diagnostic and therapeutic tools for this group on complex human disorders. http://genomemedicine.com/content/4/1/6 Corinne Richard-Miceli Lindsey Criswell Genome Medicine 2012, null:6 2012-01-27T00:00:00Z doi:10.1186/gm305 Genetic overlap in autoimmune disorders Lindsey Criswell and Corinne Richard-Miceli review risk loci that are shared among autoimmune disorders and how this information might help to explain common disease mechanisms. /content/figures/gm305-toc.gif Genome Medicine 1756-994X ${item.volume} 6 2012-01-27T00:00:00Z XML A report on the Euroepistem 2011 meeting 'Epigenomic Programming and Stem Cells for Drug Discovery', Paris, France, 21-22 November 2011. http://genomemedicine.com/content/4/1/5 Sarah Crawford Genome Medicine 2012, null:5 2012-01-27T00:00:00Z doi:10.1186/gm304 An update on stem cell therapeutics Sarah Crawford presents the highlights and roadblocks of therapeutic applications from the Euroepistem 2011 meeting on 'Epigenomic Programming and Stem Cells for Drug Discovery'. /content/figures/gm304-toc.gif Genome Medicine 1756-994X ${item.volume} 5 2012-01-27T00:00:00Z XML Side-effects are the unintended consequence of therapeutic treatments, but they can also be seen as valuable read-outs of drug effects in humans; these effects are difficult to infer or predict from pre-clinical models. Indeed, some studies suggest that drugs with similar side-effect profiles may also share therapeutic properties through related mechanisms of action. A recent publication exploits this concept to systematically investigate new indications for already marketed drugs, and presents a strategy to get the most out of the tiny portion of chemicals that have proved to be effective and safe. http://genomemedicine.com/content/4/1/3 Miquel Duran-Frigola Patrick Aloy Genome Medicine 2012, null:3 2012-01-27T00:00:00Z doi:10.1186/gm302 Side-effects as clinical markers Miquel Duran-Frigola and Patrick Aloy discuss a new computational approach to systematically exploring novel potential applications of already marketed drugs in distinct therapeutic areas. /content/figures/gm302-toc.gif Genome Medicine 1756-994X ${item.volume} 3 2012-01-27T00:00:00Z XML Background: The R620W variant in protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with rheumatoid arthritis (RA). The PTPN22 gene has alternatively spliced transcripts and at least two of the splice forms have confirmed different PTPN22 (LYP) proteins, but detailed information regarding expression of these is lacking, especially in the aspect of autoimmune diseases. Methods: We have investigated the mRNA expression of known PTPN22 splice forms with TaqMan real-time PCR in relation to ZNF592 as an endogenous reference, in peripheral blood cells from three independent cohorts with RA patients (n=139) and controls (n=111) of Caucasian origin. Polymorphisms in the PTPN22 locus (25 SNPs) and phenotypic data (gender, disease activity, ACPA and RF status) were used for analysis. Additionally we addressed possible effects of methotrexate treatment on PTPN22 expression. Results: We found consistent differences in the expression of the PTPN22 splice forms in unstimulated peripheral blood mononuclear cells between RA patients and normal controls. This difference was more pronounced when comparing the ratio of splice forms and was not affected by methotrexate treatment. Conclusions: Our data show that RA patients and healthy controls have a shift in balance of expression of splice forms derived from the PTPN22 gene. This balance seems not to be caused by treatment and may be of importance during immune response due to great structural differences in the encoded PTPN22 proteins. http://genomemedicine.com/content/4/1/2 Marcus Ronninger Yongjing Guo Klementy Shchetynsky Andrew Hill Mohsen Khademi Tomas Olsson Padmalatha Reddy Maria Seddighzadeh James Clark Lih-Ling Lin Margot O'Toole Leonid Padyukov Genome Medicine 2012, null:2 2012-01-20T00:00:00Z doi:10.1186/gm301 PTPN22 expression in rheumatoid arthritis Genotyping and phenotyping of cells from rheumatoid arthritis patients and healthy controls reveals different patterns of expression for the protein tyrosine phosphatase non-receptor 22 gene. /content/figures/gm301-toc.gif Genome Medicine 1756-994X ${item.volume} 2 2012-01-20T00:00:00Z PDF Background: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The "prostaglandin deficiency" hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission. Methods: Herein we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 +/- 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. Lipidomics platform using Ultra Performance Liquid Chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples. Results: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels which associated with decreased cognitive speed. Conclusions: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins. http://genomemedicine.com/content/4/1/1 Matej Oresic Tuulikki Seppanen-Laakso Daqiang Sun Jing Tang Sebastian Therman Rachael Viehman Ulla Mustonen Theo van Erp Tuulia Hyotylainen Paul Thompson Arthur Toga Matti Huttunen Jaana Suvisaari Jaakko Kaprio Jouko Lonnqvist Tyrone Cannon Genome Medicine 2012, null:1 2012-01-18T00:00:00Z doi:10.1186/gm300 Lipid biomarkers in schizophrenia Lipidomic, imaging and neurocognitive analysis of twin pairs reveals lipid biomarkers linked to decreased cognitive speed and potentially increased susceptibility to infection in schizophrenia. /content/figures/gm300-toc.gif Genome Medicine 1756-994X ${item.volume} 1 2012-01-18T00:00:00Z PDF