 | |
| Public | |
| Traded as | FWB: ECX |
| ISIN | DE000A11QW50 |
| Industry | Molecular Diagnostics |
| Founded | 1998 |
| Headquarters | Berlin, Germany; Seattle, Washington |
| Products | Epi proColon & Epi proLung (not available in the US). |
| Website | www |
Epigenomics AG is a molecular diagnostics company headquartered in Berlin, Germany with a wholly owned subsidiary, Epigenomics Inc. based in Seattle, WA.
Epigenomics was founded in Berlin, Germany in 1998 by serial entrepreneur Dr Alexander Olek [1] . Around the same time, ORCA Biosciences was founded in Seattle, WA. The companies merged in 2000, and have focused on applying DNA methylation based biomarkers to address medical needs. Epigenomics became a publicly traded company with its listing on the Frankfurt Exchange in 2004 raising €41.6 million. [2] The company maintains a work force in Berlin, as well as in Seattle.
Epigenomics is focused on developing and marketing molecular diagnostics for oncology. The company has discovered DNA methylation based biomarkers for a number of oncology related indications, has developed enabling technologies for the analysis of methylation in blood and other body fluids, and is bringing medically important products to the market.
Key contributions to biomarker science based on DNA methylation include:
SEPT9 - Measurement in blood for detection of colon cancer. [3] [4] [5]
SHOX2 - Measurement in lung fluid to aid in diagnosis of lung cancer. [6]
PITX2 - Measurement in prostate tissue as a prognosis factor for prostate cancer. [7]
The company continues to focus on discovering and validating DNA methylation based biomarkers, and developing the technology to make DNA methylation testing a routine practice in the clinical laboratory. Where possible, the results of these efforts are shared with the scientific community, as evidenced by >60 peer reviewed scientific publications over the past 10 years.
Epigenomics has developed and launched two CE marked IVD products based on methylation biomarkers:
These products are not currently available in the U.S.
Epigenomics has licensed the SEPT9 biomarker and certain DNA methylation technologies to Quest Diagnostics and ARUP Laboratories in the US, as well as Warnex Laboratories in Canada. These labs have independently launched Laboratory Developed Tests for the SEPT9 biomarker, and are providing this SEPT9 testing service to the medical community in the US and Canada. Although these tests were developed independently by the licensees and Epigenomics therefore cannot guarantee their performance, the results of clinical validations by these companies are very similar to those obtained by Epigenomics. Epigenomics also has a strategic partnership with Abbott Molecular for the development of an IVD test kit based on the SEPT9 biomarker. Abbott has launched this test as a CE marked IVD in Europe under the brand name mS9.
The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG islands. Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosines. Enzymes that add a methyl group are called DNA methyltransferases. In mammals, 70% to 80% of CpG cytosines are methylated. Methylating the cytosine within a gene can change its expression, a mechanism that is part of a larger field of science studying gene regulation that is called epigenetics.
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum. A cancer is the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and feeling tired all the time.
Adenocarcinoma (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.
Fecal occult blood (FOB) refers to blood in the feces that is not visibly apparent. A fecal occult blood test (FOBT) checks for hidden (occult) blood in the stool (feces). It is a screening test whose only purpose is for colorectal cancer.
Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor.
Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is usually present at very low levels in the blood of healthy adults. However, the serum levels are raised in some types of cancer, which means that it can be used as a tumor marker in clinical tests. Serum levels can also be elevated in heavy smokers.
Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky helix-distorting lesions. BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then be processed by either short-patch or long-patch BER.
Methylation specific oligonucleotide microarray, also known as MSO microarray, was developed as a technique to map epigenetic methylation changes in DNA of cancer cells.
DNA mismatch repair protein Msh2 also known as MutS homolog 2 or MSH2 is a protein that in humans is encoded by the MSH2 gene, which is located on chromosome 2. MSH2 is a tumor suppressor gene and more specifically a caretaker gene that codes for a DNA mismatch repair (MMR) protein, MSH2, which forms a heterodimer with MSH6 to make the human MutSα mismatch repair complex. It also dimerizes with MSH3 to form the MutSβ DNA repair complex. MSH2 is involved in many different forms of DNA repair, including transcription-coupled repair, homologous recombination, and base excision repair.
O6-alkylguanine DNA alkyltransferase (also known as AGT, MGMT or AGAT) is a protein that in humans is encoded by the O6-methylguanine DNA methyltransferase (MGMT) gene. O6-methylguanine DNA methyltransferase is crucial for genome stability. It repairs the naturally occurring mutagenic DNA lesion O6-methylguanine back to guanine and prevents mismatch and errors during DNA replication and transcription. Accordingly, loss of MGMT increases the carcinogenic risk in mice after exposure to alkylating agents. The two bacterial isozymes are Ada and Ogt.
Septin-9 is a protein that in humans is encoded by the SEPT9 gene.
Endonuclease VIII-like 1 is an enzyme that in humans is encoded by the NEIL1 gene.
Cancer screening aims to detect cancer before symptoms appear. This may involve blood tests, urine tests, DNA tests other tests, or medical imaging. The benefits of screening in terms of cancer prevention, early detection and subsequent treatment must be weighed against any harms.
Field cancerization is a biological process in which large areas of cells at a tissue surface or within an organ are affected by carcinogenic alterations. The process arises from exposure to an injurious environment, often over a lengthy period.
A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.
Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic alterations may be just as important, or even more important, than genetic mutations in a cell's transformation to cancer. In cancers, loss of expression of genes occurs about 10 times more frequently by transcription silencing than by mutations. As Vogelstein et al. point out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. Several medications which have epigenetic impact are now used in several of these diseases.
Cancer prevention is the practice of taking active measures to decrease the incidence of cancer and mortality. The practice of prevention is dependent upon both individual efforts to improve lifestyle and seek preventive screening, and socioeconomic or public policy related to cancer prevention. Globalized cancer prevention is regarded as a critical objective due to its applicability to large populations, reducing long term effects of cancer by promoting proactive health practices and behaviors, and its perceived cost-effectiveness and viability for all socioeconomic classes.
Generally, in progression to cancer, hundreds of genes are silenced or activated. Although silencing of some genes in cancers occurs by mutation, a large proportion of carcinogenic gene silencing is a result of altered DNA methylation. DNA methylation causing silencing in cancer typically occurs at multiple CpG sites in the CpG islands that are present in the promoters of protein coding genes.
DNA methylation in cancer plays a variety of roles, helping to change the healthy regulation of gene expression to a disease pattern.
Glal hydrolysis and Ligation Adapter Dependent PCR assay is the novel method to determine R(5mC)GY sites produced in the course of de novo DNA methylation with DNMTЗA and DNMTЗB DNA methyltransferases. GLAD-PCR assay do not require bisulfite treatment of the DNA.
