Epigenomics AG Delivers Clinical Proof-of-Concept for Lung Cancer Detection

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Epigenomics AG (Frankfurt:ECX) today announced that it has procured positive results from a clinical trial investigating the feasibility of a test to detect patients with non-small cell lung cancer (NSCLC).

The program aims at developing a blood based test for the reliable and convenient early detection of lung cancer. In an initial study last year Epigenomics identified numerous candidate DNA methylation biomarkers that appear in lung tumors, but not in normal lung tissue. The objective of this most recent study, run in cooperation with the Department of Pneumology at the Charite in Berlin headed by Prof. Dr. Christian Witt, was to show that the most promising candidate biomarker identified previously can also be detected in blood plasma of lung cancer patients. This is an important prerequisite for developing a convenient blood based early detection test for this cancer. The study was carried out on a group of patients with either lung cancer or benign lung disease. The study came to the result that the most promising candidate biomarker detects patients with lung cancer, and differentiates them from individuals with positive computer tomography (CT) due to non-cancerous lung diseases. Based on this proprietary novel DNA methylation biomarker and the encouraging results, Epigenomics will continue the development of its lung cancer screening test. With these results in lung cancer, Epigenomics has achieved clinical proof-of-concept in the third major cancer indication, after successful clinical studies in colorectal cancer and prostate cancer screening programs.

Lung cancer is responsible for approximately 1.3 million deaths worldwide annually, and accounts for the most deaths of any cancer. Epigenomics notes that most lung cancer patients are currently diagnosed when their disease is advanced, and nealy 90 percent die within two years. An effective blood-based screening test for lung cancer would be a tremendous advance for aiding in the early detection and improved treatment options for lung cancer patients. Link

Epigenetics Receives Green Light as Major Initiative in NIH Roadmap 1.5

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The National Institutes of Health (NIH) has concluded their selection process for a new cohort of Roadmap initiatives, approving four topics as Major Roadmap Initiatives. Two programs, epigenetics and microbiomes, were approved for immediate implementation as five year programs. The four programs approved as major roadmap initiatives are:

Microbiome – The goal of the proposed Human Microbiome Project is to characterize the microbial content of sites in the human body and examine whether changes in the microbiome can be related to disease.

Epigenetics – Epigenetics is the study of stable genetic modifications that result in changes in gene expression and function without a corresponding alteration in DNA sequence. The epigenome is a catalog of the epigenetic modifications that occur in the genome. Epigenetic changes have been associated with disease, but further progress requires the development of better methods to detect the modifications and a clearer understanding of factors that drive these changes.

Protein Capture Tools/ Proteome Tools – The Proteome is the complete set of proteins in the body. Efforts in this area would support developing and making available to the scientific community high quality probes specific to every protein in the human and in desired animal models. This would allow the ability to characterize protein function in health and disease and to monitor the markers of a disease in order to deploy early prevention efforts and to identify potential therapeutic targets.

Phenotyping Services and Tools – A human Phenotype is the total physical appearance and constitution of a person, often determined by multiple genes and influenced by environmental interactions. Initiatives in this area would encourage the development of resources to systematically catalog human phenotypes in an effort to characterize complex diseases and disorders. Link

Science reports that NIH will be sending out solicitations for the epigenetics and microbiome initiatives this fall. Link

Epigenetic Natural Variation in Arabidopsis thaliana

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A new research paper appearing today in PLoS Biology provides new insight into the DNA methylation patterns in the plant Araabidopsis thaliana:

Cytosine methylation of repetitive sequences is widespread in plant genomes, occurring in both symmetric (CpG and CpNpG) as well as asymmetric sequence contexts. We used the methylation-dependent restriction enzyme McrBC to profile methylated DNA using tiling microarrays of Arabidopsis Chromosome 4 in two distinct ecotypes, Columbia and Landsberg erecta. We also used comparative genome hybridization to profile copy number polymorphisms. Repeated sequences and transposable elements (TEs), especially long terminal repeat retrotransposons, are densely methylated, but one third of genes also have low but detectable methylation in their transcribed regions. While TEs are almost always methylated, genic methylation is highly polymorphic, with half of all methylated genes being methylated in only one of the two ecotypes. A survey of loci in 96 Arabidopsis accessions revealed a similar degree of methylation polymorphism. Within-gene methylation is heritable, but is lost at a high frequency in segregating F2 families. Promoter methylation is rare, and gene expression is not generally affected by differences in DNA methylation. Small interfering RNA are preferentially associated with methylated TEs, but not with methylated genes, indicating that most genic methylation is not guided by small interfering RNA. This may account for the instability of gene methylation, if occasional failure of maintenance methylation cannot be restored by other means.


CpG Methylation Targeted to Transcription Units in an Invertebrate Genome

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I just came across an interesting research paper by Suzuki et al. in a recent issue of Genome Research: CpG methylation is targeted to transcription units in an invertebrate genome.

DNA is methylated at the dinucleotide CpG in genomes of a wide range of plants and animals. Among animals, variable patterns of genomic CpG methylation have been described, ranging from undetectable levels (e.g., in Caenorhabditis elegans) to high levels of global methylation in the vertebrates. The most frequent pattern in invertebrate animals, however, is mosaic methylation, comprising domains of methylated DNA interspersed with unmethylated domains. To understand the origin of mosaic DNA methylation patterns, we examined the distribution of DNA methylation in the Ciona intestinalis genome. Bisulfite sequencing and computational analysis revealed methylated domains with sharp boundaries that strongly colocalize with 60% of transcription units. By contrast, promoters, intergenic DNA, and transposons are not preferentially targeted by DNA methylation. Methylated transcription units include evolutionarily conserved genes, whereas the most highly expressed genes preferentially belong to the unmethylated fraction. The results lend support to the hypothesis that CpG methylation functions to suppress spurious transcriptional initiation within infrequently transcribed genes.

The article is freely accessible to all. Link

Role of the Polycomb Repressive Complex 2 in Acute Promyelocytic Leukemia

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New research published today in the journal Cancer Cell by Villa et al. sheds new light on the interaction between two gene regulation mechanisms: DNA methylation and the Polycomb protein complex.

Epigenetic changes are common alterations in cancer cells. Here, we have investigated the role of Polycomb group proteins in the establishment and maintenance of the aberrant silencing of tumor suppressor genes during transformation induced by the leukemia-associated PML-RAR fusion protein. We show that in leukemic cells knockdown of SUZ12, a key component of Polycomb repressive complex 2 (PRC2), reverts not only histone modification but also induces DNA demethylation of PML-RAR target genes. This results in promoter reactivation and granulocytic differentiation. Importantly, the epigenetic alterations caused by PML-RAR can be reverted by retinoic acid treatment of primary blasts from leukemic patients. Our results demonstrate that the direct targeting of Polycomb group proteins by an oncogene plays a key role during carcinogenesis.

innovations-report has a nice summary of previous work done in this area and the significance of the current paper.

The featured article in the June issue is available for free. Link

Coming Soon: Broad Epigenetic Product Library from Sigma-Aldrich

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This morning Sigma-Aldrich announced that it has signed a licensing agreement with Epigentek Group, Inc. for core technologies in DNA modification, methylation quantification and protein/DNA interaction. The first product, the Imprint DNA Modification Kit, is available starting this month. Sigma will also be offering kits for global methylation quantitation and chromatin immunoprecipitation based on Epigentek’s technologies.

Epigentek offers the most sensitive, reliable and fastest procedures for Bisulfite DNA modification and chromatin immunoprecipitation. Their proprietary DNA modification technology provides DNA conversion for methylation analysis in less than two hours and requires only 50 picograms of starting DNA.


The DNA Network: Rapidly Expanding

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The DNA Network was launched about a month ago with 12 blogs joining together to offer a network feed and other communication between bloggers. Since then, 5 other blogs have joined the network:

I have discovered some great new voices through the network. Maybe you’ll find something worth reading in the network, too.

Free Epigenetics News Career Board Goes Live

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Since launching Epigenetics News in March 2006, I have received countless e-mails from companies and laboratories requesting information on posting an open position at the blog. On a few occasions I have posted the job opening here, but after looking for a better solution I chose to set up a separate job board for epigenetics-related positions.

Meet the Epigenetics News Career Board: Any employer worldwide that is looking to fill a position that requires epigenomics experience, or is related to the field of epigenetics, can post their job listing for FREE.

As of this posting, there are two positions posted, including the aforementioned scientist position at Affinity Scientific in San Diego, CA, and a new postdoctoral scientist position at the Baker Medical Research Laboratory in Melbourne, Australia.

If you’re seeking or looking to fill an epigenetics-related position, head to the Epigenetics News Career Board.

Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii

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A new research article appeared today in the open access journal PLoS Pathogens with new insights into the epigenetics modifications regulating gene expression in the human pathogen Toxoplasma gondii:

Apicomplexan parasites, including Toxoplasma gondii, are responsible for a variety of deadly infections, but little is understood about how these important pathogens regulate gene expression. Initial studies suggest that alterations in chromatin structure regulate expression of virulence traits. To understand the relationship of chromatin remodeling and transcriptional regulation in T. gondii, we characterized the histone modifications and gene expression of a contiguous 1% of the T. gondii genome using custom DNA oligonucleotide microarrays. We found that active promoters have a characteristic pattern of histone modifications that correlates strongly with active gene expression in tachyzoites. These data, integrated with prior gene predictions, enable more accurate annotation of the genome and discovery of new genes. Further, these studies illustrate the power of an integrated epigenomic approach to illuminate the role of the “histone code” in regulation of gene expression in the Apicomplexa.


Looking for a Guest Blogger

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So summer rolls around, and I expected to have more time for blogging, but it just hasn’t happened yet. I am working in the lab full-time and it has been very busy, as always. There are lots of things to take care of at home that were put off during the academic semesters in lieu of studying and keeping up my lab responsibilities. So it has been a pretty hectic summer thus far and the blog has not seen much activity as a result.

However, I hope to change that over the next few weeks.

I have a week-long family vacation planned for the first week of July (June 30-July 7), and I figured that it may be as good a time as any to try offering a “guest blogger” here at Epigenetics News. So, if you have some idea of epigenetics and want to have a week-long opportunity to write about to an audience that’s very interested in the topic, get in touch with me at admin [at] epigeneticsnews [dot] com. Ideally, this person would be someone who does epigenetics research or has done blogging on the topic before, but don’t let that stop you from applying.

Just type up a quick e-mail and we’ll get the process started.